Genomically amplified Akt3 activates DNA repair pathway and promotes glioma progression
Akt is a robust oncogene that plays key roles in the development and progression of many cancers, including glioma. We evaluated the differential propensities of the Akt isoforms toward progression in the well-characterized RCAS/Ntv-a mouse model of PDGFB-driven low grade glioma. A constitutively ac...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
David E. Cogdell [verfasserIn] |
|---|
| Format: |
Artikel |
|---|---|
| Sprache: |
Englisch |
| Erschienen: |
2015 |
|---|
| Rechteinformationen: |
Nutzungsrecht: © COPYRIGHT 2015 National Academy of Sciences |
|---|
| Übergeordnetes Werk: |
Enthalten in: Proceedings of the National Academy of Sciences of the United States of America - Washington, DC : NAS, 1877, 112(2015), 11, Seite 3421-3426 |
|---|---|
| Übergeordnetes Werk: |
volume:112 ; year:2015 ; number:11 ; pages:3421-3426 |
| Links: |
Volltext |
|---|
| DOI / URN: |
10.1073/pnas.1414573112 |
|---|
| Katalog-ID: |
OLC1970258969 |
|---|
| LEADER | 01000caa a2200265 4500 | ||
|---|---|---|---|
| 001 | OLC1970258969 | ||
| 003 | DE-627 | ||
| 005 | 20230714175846.0 | ||
| 007 | tu | ||
| 008 | 160211s2015 xx ||||| 00| ||eng c | ||
| 024 | 7 | |a 10.1073/pnas.1414573112 |2 doi | |
| 028 | 5 | 2 | |a PQ20160211 |
| 035 | |a (DE-627)OLC1970258969 | ||
| 035 | |a (DE-599)GBVOLC1970258969 | ||
| 035 | |a (PRQ)c3056-414d47b6346f5ea0577f03f9d7ba8d02c0111186f8d2ab949b93165e369d71423 | ||
| 035 | |a (KEY)0583363920150000112001103421genomicallyamplifiedakt3activatesdnarepairpathwaya | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 082 | 0 | 4 | |a 500 |q DNB |
| 082 | 0 | 4 | |a 570 |q AVZ |
| 084 | |a LING |2 fid | ||
| 084 | |a BIODIV |2 fid | ||
| 100 | 0 | |a David E. Cogdell |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Genomically amplified Akt3 activates DNA repair pathway and promotes glioma progression |
| 264 | 1 | |c 2015 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 520 | |a Akt is a robust oncogene that plays key roles in the development and progression of many cancers, including glioma. We evaluated the differential propensities of the Akt isoforms toward progression in the well-characterized RCAS/Ntv-a mouse model of PDGFB-driven low grade glioma. A constitutively active myristoylated form of Akt1 did not induce high-grade glioma (HGG). In stark contrast, Akt2 and Akt3 showed strong progression potential with 78% and 97% of tumors diagnosed as HGG, respectively. We further revealed that significant variations in polarity and hydropathy values among the Akt isoforms in both the pleckstrin homology domain (P domain) and regulatory domain (R domain) were critical in mediating glioma progression. Gene expression profiles from representative Akt-derived tumors indicated dominant and distinct roles for Akt3, consisting primarily of DNA repair pathways. TCGA data from human GBM closely reflected the DNA repair function, as Akt3 was significantly correlated with a 76-gene signature DNA repair panel. Consistently, compared with Akt1 and Akt2 overexpression models, Akt3-expressing human GBM cells had enhanced activation of DNA repair proteins, leading to increased DNA repair and subsequent resistance to radiation and temozolomide. Given the wide range of Akt3-amplified cancers, Akt3 may represent a key resistance factor. | ||
| 540 | |a Nutzungsrecht: © COPYRIGHT 2015 National Academy of Sciences | ||
| 650 | 4 | |a Signal Transduction - radiation effects | |
| 650 | 4 | |a Gene Amplification - drug effects | |
| 650 | 4 | |a Glioma - enzymology | |
| 650 | 4 | |a Dacarbazine - therapeutic use | |
| 650 | 4 | |a Brain Neoplasms - enzymology | |
| 650 | 4 | |a Glioma - genetics | |
| 650 | 4 | |a DNA Repair - drug effects | |
| 650 | 4 | |a DNA Damage - genetics | |
| 650 | 4 | |a Isoenzymes - chemistry | |
| 650 | 4 | |a Drug Resistance, Neoplasm - drug effects | |
| 650 | 4 | |a DNA Repair - radiation effects | |
| 650 | 4 | |a Signal Transduction - drug effects | |
| 650 | 4 | |a Signal Transduction - genetics | |
| 650 | 4 | |a Radiation Tolerance - genetics | |
| 650 | 4 | |a Proto-Oncogene Proteins c-akt - chemistry | |
| 650 | 4 | |a Gene Amplification - radiation effects | |
| 650 | 4 | |a Isoenzymes - metabolism | |
| 650 | 4 | |a Brain Neoplasms - genetics | |
| 650 | 4 | |a Dacarbazine - pharmacology | |
| 650 | 4 | |a Proto-Oncogene Proteins c-akt - genetics | |
| 650 | 4 | |a DNA Repair - genetics | |
| 650 | 4 | |a Isoenzymes - genetics | |
| 650 | 4 | |a Brain Neoplasms - pathology | |
| 650 | 4 | |a Drug Resistance, Neoplasm - radiation effects | |
| 650 | 4 | |a Glioma - pathology | |
| 650 | 4 | |a Drug Resistance, Neoplasm - genetics | |
| 650 | 4 | |a Proto-Oncogene Proteins c-akt - metabolism | |
| 650 | 4 | |a Dacarbazine - analogs & derivatives | |
| 650 | 4 | |a Deoxyribonucleic acid--DNA | |
| 650 | 4 | |a Gene expression | |
| 650 | 4 | |a Tumors | |
| 650 | 4 | |a DNA repair | |
| 650 | 4 | |a Gene amplification | |
| 650 | 4 | |a Genomics | |
| 650 | 4 | |a glioma | |
| 650 | 4 | |a RCAS | |
| 650 | 4 | |a tv-a mouse model | |
| 650 | 4 | |a Biological Sciences | |
| 650 | 4 | |a Akt | |
| 700 | 0 | |a Olli Yli-Harja |4 oth | |
| 700 | 0 | |a Matti Nykter |4 oth | |
| 700 | 0 | |a Youting Sun |4 oth | |
| 700 | 0 | |a Xinhui Zhou |4 oth | |
| 700 | 0 | |a Kristen M. Turner |4 oth | |
| 700 | 0 | |a W. K. Alfred Yung |4 oth | |
| 700 | 0 | |a Brady Bernard |4 oth | |
| 700 | 0 | |a Gregory N. Fuller |4 oth | |
| 700 | 0 | |a Ping Ji |4 oth | |
| 700 | 0 | |a Kirsi J. Granberg |4 oth | |
| 700 | 0 | |a Wei Zhang |4 oth | |
| 700 | 0 | |a Limei Hu |4 oth | |
| 700 | 0 | |a Ilya Shmulevich |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |t Proceedings of the National Academy of Sciences of the United States of America |d Washington, DC : NAS, 1877 |g 112(2015), 11, Seite 3421-3426 |w (DE-627)129505269 |w (DE-600)209104-5 |w (DE-576)014909189 |x 0027-8424 |7 nnns |
| 773 | 1 | 8 | |g volume:112 |g year:2015 |g number:11 |g pages:3421-3426 |
| 856 | 4 | 1 | |u http://dx.doi.org/10.1073/pnas.1414573112 |3 Volltext |
| 856 | 4 | 2 | |u http://www.pnas.org/content/112/11/3421.abstract |
| 856 | 4 | 2 | |u http://www.ncbi.nlm.nih.gov/pubmed/25737557 |
| 856 | 4 | 2 | |u http://search.proquest.com/docview/1665573221 |
| 856 | 4 | 2 | |u http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4371922&tool=pmcentrez&rendertype=abstract |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a SYSFLAG_A | ||
| 912 | |a GBV_OLC | ||
| 912 | |a FID-LING | ||
| 912 | |a FID-BIODIV | ||
| 912 | |a SSG-OLC-PHY | ||
| 912 | |a SSG-OLC-CHE | ||
| 912 | |a SSG-OLC-MAT | ||
| 912 | |a SSG-OLC-FOR | ||
| 912 | |a SSG-OLC-PHA | ||
| 912 | |a SSG-OLC-DE-84 | ||
| 912 | |a SSG-OPC-MAT | ||
| 912 | |a SSG-OPC-FOR | ||
| 912 | |a GBV_ILN_40 | ||
| 912 | |a GBV_ILN_59 | ||
| 951 | |a AR | ||
| 952 | |d 112 |j 2015 |e 11 |h 3421-3426 | ||
| author_variant |
d e c dec |
|---|---|
| matchkey_str |
article:00278424:2015----::eoialapiidk3ciaedaearahaadrm |
| hierarchy_sort_str |
2015 |
| publishDate |
2015 |
| allfields |
10.1073/pnas.1414573112 doi PQ20160211 (DE-627)OLC1970258969 (DE-599)GBVOLC1970258969 (PRQ)c3056-414d47b6346f5ea0577f03f9d7ba8d02c0111186f8d2ab949b93165e369d71423 (KEY)0583363920150000112001103421genomicallyamplifiedakt3activatesdnarepairpathwaya DE-627 ger DE-627 rakwb eng 500 DNB 570 AVZ LING fid BIODIV fid David E. Cogdell verfasserin aut Genomically amplified Akt3 activates DNA repair pathway and promotes glioma progression 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Akt is a robust oncogene that plays key roles in the development and progression of many cancers, including glioma. We evaluated the differential propensities of the Akt isoforms toward progression in the well-characterized RCAS/Ntv-a mouse model of PDGFB-driven low grade glioma. A constitutively active myristoylated form of Akt1 did not induce high-grade glioma (HGG). In stark contrast, Akt2 and Akt3 showed strong progression potential with 78% and 97% of tumors diagnosed as HGG, respectively. We further revealed that significant variations in polarity and hydropathy values among the Akt isoforms in both the pleckstrin homology domain (P domain) and regulatory domain (R domain) were critical in mediating glioma progression. Gene expression profiles from representative Akt-derived tumors indicated dominant and distinct roles for Akt3, consisting primarily of DNA repair pathways. TCGA data from human GBM closely reflected the DNA repair function, as Akt3 was significantly correlated with a 76-gene signature DNA repair panel. Consistently, compared with Akt1 and Akt2 overexpression models, Akt3-expressing human GBM cells had enhanced activation of DNA repair proteins, leading to increased DNA repair and subsequent resistance to radiation and temozolomide. Given the wide range of Akt3-amplified cancers, Akt3 may represent a key resistance factor. Nutzungsrecht: © COPYRIGHT 2015 National Academy of Sciences Signal Transduction - radiation effects Gene Amplification - drug effects Glioma - enzymology Dacarbazine - therapeutic use Brain Neoplasms - enzymology Glioma - genetics DNA Repair - drug effects DNA Damage - genetics Isoenzymes - chemistry Drug Resistance, Neoplasm - drug effects DNA Repair - radiation effects Signal Transduction - drug effects Signal Transduction - genetics Radiation Tolerance - genetics Proto-Oncogene Proteins c-akt - chemistry Gene Amplification - radiation effects Isoenzymes - metabolism Brain Neoplasms - genetics Dacarbazine - pharmacology Proto-Oncogene Proteins c-akt - genetics DNA Repair - genetics Isoenzymes - genetics Brain Neoplasms - pathology Drug Resistance, Neoplasm - radiation effects Glioma - pathology Drug Resistance, Neoplasm - genetics Proto-Oncogene Proteins c-akt - metabolism Dacarbazine - analogs & derivatives Deoxyribonucleic acid--DNA Gene expression Tumors DNA repair Gene amplification Genomics glioma RCAS tv-a mouse model Biological Sciences Akt Olli Yli-Harja oth Matti Nykter oth Youting Sun oth Xinhui Zhou oth Kristen M. Turner oth W. K. Alfred Yung oth Brady Bernard oth Gregory N. Fuller oth Ping Ji oth Kirsi J. Granberg oth Wei Zhang oth Limei Hu oth Ilya Shmulevich oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 112(2015), 11, Seite 3421-3426 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:112 year:2015 number:11 pages:3421-3426 http://dx.doi.org/10.1073/pnas.1414573112 Volltext http://www.pnas.org/content/112/11/3421.abstract http://www.ncbi.nlm.nih.gov/pubmed/25737557 http://search.proquest.com/docview/1665573221 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4371922&tool=pmcentrez&rendertype=abstract GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 112 2015 11 3421-3426 |
| spelling |
10.1073/pnas.1414573112 doi PQ20160211 (DE-627)OLC1970258969 (DE-599)GBVOLC1970258969 (PRQ)c3056-414d47b6346f5ea0577f03f9d7ba8d02c0111186f8d2ab949b93165e369d71423 (KEY)0583363920150000112001103421genomicallyamplifiedakt3activatesdnarepairpathwaya DE-627 ger DE-627 rakwb eng 500 DNB 570 AVZ LING fid BIODIV fid David E. Cogdell verfasserin aut Genomically amplified Akt3 activates DNA repair pathway and promotes glioma progression 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Akt is a robust oncogene that plays key roles in the development and progression of many cancers, including glioma. We evaluated the differential propensities of the Akt isoforms toward progression in the well-characterized RCAS/Ntv-a mouse model of PDGFB-driven low grade glioma. A constitutively active myristoylated form of Akt1 did not induce high-grade glioma (HGG). In stark contrast, Akt2 and Akt3 showed strong progression potential with 78% and 97% of tumors diagnosed as HGG, respectively. We further revealed that significant variations in polarity and hydropathy values among the Akt isoforms in both the pleckstrin homology domain (P domain) and regulatory domain (R domain) were critical in mediating glioma progression. Gene expression profiles from representative Akt-derived tumors indicated dominant and distinct roles for Akt3, consisting primarily of DNA repair pathways. TCGA data from human GBM closely reflected the DNA repair function, as Akt3 was significantly correlated with a 76-gene signature DNA repair panel. Consistently, compared with Akt1 and Akt2 overexpression models, Akt3-expressing human GBM cells had enhanced activation of DNA repair proteins, leading to increased DNA repair and subsequent resistance to radiation and temozolomide. Given the wide range of Akt3-amplified cancers, Akt3 may represent a key resistance factor. Nutzungsrecht: © COPYRIGHT 2015 National Academy of Sciences Signal Transduction - radiation effects Gene Amplification - drug effects Glioma - enzymology Dacarbazine - therapeutic use Brain Neoplasms - enzymology Glioma - genetics DNA Repair - drug effects DNA Damage - genetics Isoenzymes - chemistry Drug Resistance, Neoplasm - drug effects DNA Repair - radiation effects Signal Transduction - drug effects Signal Transduction - genetics Radiation Tolerance - genetics Proto-Oncogene Proteins c-akt - chemistry Gene Amplification - radiation effects Isoenzymes - metabolism Brain Neoplasms - genetics Dacarbazine - pharmacology Proto-Oncogene Proteins c-akt - genetics DNA Repair - genetics Isoenzymes - genetics Brain Neoplasms - pathology Drug Resistance, Neoplasm - radiation effects Glioma - pathology Drug Resistance, Neoplasm - genetics Proto-Oncogene Proteins c-akt - metabolism Dacarbazine - analogs & derivatives Deoxyribonucleic acid--DNA Gene expression Tumors DNA repair Gene amplification Genomics glioma RCAS tv-a mouse model Biological Sciences Akt Olli Yli-Harja oth Matti Nykter oth Youting Sun oth Xinhui Zhou oth Kristen M. Turner oth W. K. Alfred Yung oth Brady Bernard oth Gregory N. Fuller oth Ping Ji oth Kirsi J. Granberg oth Wei Zhang oth Limei Hu oth Ilya Shmulevich oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 112(2015), 11, Seite 3421-3426 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:112 year:2015 number:11 pages:3421-3426 http://dx.doi.org/10.1073/pnas.1414573112 Volltext http://www.pnas.org/content/112/11/3421.abstract http://www.ncbi.nlm.nih.gov/pubmed/25737557 http://search.proquest.com/docview/1665573221 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4371922&tool=pmcentrez&rendertype=abstract GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 112 2015 11 3421-3426 |
| allfields_unstemmed |
10.1073/pnas.1414573112 doi PQ20160211 (DE-627)OLC1970258969 (DE-599)GBVOLC1970258969 (PRQ)c3056-414d47b6346f5ea0577f03f9d7ba8d02c0111186f8d2ab949b93165e369d71423 (KEY)0583363920150000112001103421genomicallyamplifiedakt3activatesdnarepairpathwaya DE-627 ger DE-627 rakwb eng 500 DNB 570 AVZ LING fid BIODIV fid David E. Cogdell verfasserin aut Genomically amplified Akt3 activates DNA repair pathway and promotes glioma progression 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Akt is a robust oncogene that plays key roles in the development and progression of many cancers, including glioma. We evaluated the differential propensities of the Akt isoforms toward progression in the well-characterized RCAS/Ntv-a mouse model of PDGFB-driven low grade glioma. A constitutively active myristoylated form of Akt1 did not induce high-grade glioma (HGG). In stark contrast, Akt2 and Akt3 showed strong progression potential with 78% and 97% of tumors diagnosed as HGG, respectively. We further revealed that significant variations in polarity and hydropathy values among the Akt isoforms in both the pleckstrin homology domain (P domain) and regulatory domain (R domain) were critical in mediating glioma progression. Gene expression profiles from representative Akt-derived tumors indicated dominant and distinct roles for Akt3, consisting primarily of DNA repair pathways. TCGA data from human GBM closely reflected the DNA repair function, as Akt3 was significantly correlated with a 76-gene signature DNA repair panel. Consistently, compared with Akt1 and Akt2 overexpression models, Akt3-expressing human GBM cells had enhanced activation of DNA repair proteins, leading to increased DNA repair and subsequent resistance to radiation and temozolomide. Given the wide range of Akt3-amplified cancers, Akt3 may represent a key resistance factor. Nutzungsrecht: © COPYRIGHT 2015 National Academy of Sciences Signal Transduction - radiation effects Gene Amplification - drug effects Glioma - enzymology Dacarbazine - therapeutic use Brain Neoplasms - enzymology Glioma - genetics DNA Repair - drug effects DNA Damage - genetics Isoenzymes - chemistry Drug Resistance, Neoplasm - drug effects DNA Repair - radiation effects Signal Transduction - drug effects Signal Transduction - genetics Radiation Tolerance - genetics Proto-Oncogene Proteins c-akt - chemistry Gene Amplification - radiation effects Isoenzymes - metabolism Brain Neoplasms - genetics Dacarbazine - pharmacology Proto-Oncogene Proteins c-akt - genetics DNA Repair - genetics Isoenzymes - genetics Brain Neoplasms - pathology Drug Resistance, Neoplasm - radiation effects Glioma - pathology Drug Resistance, Neoplasm - genetics Proto-Oncogene Proteins c-akt - metabolism Dacarbazine - analogs & derivatives Deoxyribonucleic acid--DNA Gene expression Tumors DNA repair Gene amplification Genomics glioma RCAS tv-a mouse model Biological Sciences Akt Olli Yli-Harja oth Matti Nykter oth Youting Sun oth Xinhui Zhou oth Kristen M. Turner oth W. K. Alfred Yung oth Brady Bernard oth Gregory N. Fuller oth Ping Ji oth Kirsi J. Granberg oth Wei Zhang oth Limei Hu oth Ilya Shmulevich oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 112(2015), 11, Seite 3421-3426 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:112 year:2015 number:11 pages:3421-3426 http://dx.doi.org/10.1073/pnas.1414573112 Volltext http://www.pnas.org/content/112/11/3421.abstract http://www.ncbi.nlm.nih.gov/pubmed/25737557 http://search.proquest.com/docview/1665573221 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4371922&tool=pmcentrez&rendertype=abstract GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 112 2015 11 3421-3426 |
| allfieldsGer |
10.1073/pnas.1414573112 doi PQ20160211 (DE-627)OLC1970258969 (DE-599)GBVOLC1970258969 (PRQ)c3056-414d47b6346f5ea0577f03f9d7ba8d02c0111186f8d2ab949b93165e369d71423 (KEY)0583363920150000112001103421genomicallyamplifiedakt3activatesdnarepairpathwaya DE-627 ger DE-627 rakwb eng 500 DNB 570 AVZ LING fid BIODIV fid David E. Cogdell verfasserin aut Genomically amplified Akt3 activates DNA repair pathway and promotes glioma progression 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Akt is a robust oncogene that plays key roles in the development and progression of many cancers, including glioma. We evaluated the differential propensities of the Akt isoforms toward progression in the well-characterized RCAS/Ntv-a mouse model of PDGFB-driven low grade glioma. A constitutively active myristoylated form of Akt1 did not induce high-grade glioma (HGG). In stark contrast, Akt2 and Akt3 showed strong progression potential with 78% and 97% of tumors diagnosed as HGG, respectively. We further revealed that significant variations in polarity and hydropathy values among the Akt isoforms in both the pleckstrin homology domain (P domain) and regulatory domain (R domain) were critical in mediating glioma progression. Gene expression profiles from representative Akt-derived tumors indicated dominant and distinct roles for Akt3, consisting primarily of DNA repair pathways. TCGA data from human GBM closely reflected the DNA repair function, as Akt3 was significantly correlated with a 76-gene signature DNA repair panel. Consistently, compared with Akt1 and Akt2 overexpression models, Akt3-expressing human GBM cells had enhanced activation of DNA repair proteins, leading to increased DNA repair and subsequent resistance to radiation and temozolomide. Given the wide range of Akt3-amplified cancers, Akt3 may represent a key resistance factor. Nutzungsrecht: © COPYRIGHT 2015 National Academy of Sciences Signal Transduction - radiation effects Gene Amplification - drug effects Glioma - enzymology Dacarbazine - therapeutic use Brain Neoplasms - enzymology Glioma - genetics DNA Repair - drug effects DNA Damage - genetics Isoenzymes - chemistry Drug Resistance, Neoplasm - drug effects DNA Repair - radiation effects Signal Transduction - drug effects Signal Transduction - genetics Radiation Tolerance - genetics Proto-Oncogene Proteins c-akt - chemistry Gene Amplification - radiation effects Isoenzymes - metabolism Brain Neoplasms - genetics Dacarbazine - pharmacology Proto-Oncogene Proteins c-akt - genetics DNA Repair - genetics Isoenzymes - genetics Brain Neoplasms - pathology Drug Resistance, Neoplasm - radiation effects Glioma - pathology Drug Resistance, Neoplasm - genetics Proto-Oncogene Proteins c-akt - metabolism Dacarbazine - analogs & derivatives Deoxyribonucleic acid--DNA Gene expression Tumors DNA repair Gene amplification Genomics glioma RCAS tv-a mouse model Biological Sciences Akt Olli Yli-Harja oth Matti Nykter oth Youting Sun oth Xinhui Zhou oth Kristen M. Turner oth W. K. Alfred Yung oth Brady Bernard oth Gregory N. Fuller oth Ping Ji oth Kirsi J. Granberg oth Wei Zhang oth Limei Hu oth Ilya Shmulevich oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 112(2015), 11, Seite 3421-3426 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:112 year:2015 number:11 pages:3421-3426 http://dx.doi.org/10.1073/pnas.1414573112 Volltext http://www.pnas.org/content/112/11/3421.abstract http://www.ncbi.nlm.nih.gov/pubmed/25737557 http://search.proquest.com/docview/1665573221 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4371922&tool=pmcentrez&rendertype=abstract GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 112 2015 11 3421-3426 |
| allfieldsSound |
10.1073/pnas.1414573112 doi PQ20160211 (DE-627)OLC1970258969 (DE-599)GBVOLC1970258969 (PRQ)c3056-414d47b6346f5ea0577f03f9d7ba8d02c0111186f8d2ab949b93165e369d71423 (KEY)0583363920150000112001103421genomicallyamplifiedakt3activatesdnarepairpathwaya DE-627 ger DE-627 rakwb eng 500 DNB 570 AVZ LING fid BIODIV fid David E. Cogdell verfasserin aut Genomically amplified Akt3 activates DNA repair pathway and promotes glioma progression 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Akt is a robust oncogene that plays key roles in the development and progression of many cancers, including glioma. We evaluated the differential propensities of the Akt isoforms toward progression in the well-characterized RCAS/Ntv-a mouse model of PDGFB-driven low grade glioma. A constitutively active myristoylated form of Akt1 did not induce high-grade glioma (HGG). In stark contrast, Akt2 and Akt3 showed strong progression potential with 78% and 97% of tumors diagnosed as HGG, respectively. We further revealed that significant variations in polarity and hydropathy values among the Akt isoforms in both the pleckstrin homology domain (P domain) and regulatory domain (R domain) were critical in mediating glioma progression. Gene expression profiles from representative Akt-derived tumors indicated dominant and distinct roles for Akt3, consisting primarily of DNA repair pathways. TCGA data from human GBM closely reflected the DNA repair function, as Akt3 was significantly correlated with a 76-gene signature DNA repair panel. Consistently, compared with Akt1 and Akt2 overexpression models, Akt3-expressing human GBM cells had enhanced activation of DNA repair proteins, leading to increased DNA repair and subsequent resistance to radiation and temozolomide. Given the wide range of Akt3-amplified cancers, Akt3 may represent a key resistance factor. Nutzungsrecht: © COPYRIGHT 2015 National Academy of Sciences Signal Transduction - radiation effects Gene Amplification - drug effects Glioma - enzymology Dacarbazine - therapeutic use Brain Neoplasms - enzymology Glioma - genetics DNA Repair - drug effects DNA Damage - genetics Isoenzymes - chemistry Drug Resistance, Neoplasm - drug effects DNA Repair - radiation effects Signal Transduction - drug effects Signal Transduction - genetics Radiation Tolerance - genetics Proto-Oncogene Proteins c-akt - chemistry Gene Amplification - radiation effects Isoenzymes - metabolism Brain Neoplasms - genetics Dacarbazine - pharmacology Proto-Oncogene Proteins c-akt - genetics DNA Repair - genetics Isoenzymes - genetics Brain Neoplasms - pathology Drug Resistance, Neoplasm - radiation effects Glioma - pathology Drug Resistance, Neoplasm - genetics Proto-Oncogene Proteins c-akt - metabolism Dacarbazine - analogs & derivatives Deoxyribonucleic acid--DNA Gene expression Tumors DNA repair Gene amplification Genomics glioma RCAS tv-a mouse model Biological Sciences Akt Olli Yli-Harja oth Matti Nykter oth Youting Sun oth Xinhui Zhou oth Kristen M. Turner oth W. K. Alfred Yung oth Brady Bernard oth Gregory N. Fuller oth Ping Ji oth Kirsi J. Granberg oth Wei Zhang oth Limei Hu oth Ilya Shmulevich oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 112(2015), 11, Seite 3421-3426 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:112 year:2015 number:11 pages:3421-3426 http://dx.doi.org/10.1073/pnas.1414573112 Volltext http://www.pnas.org/content/112/11/3421.abstract http://www.ncbi.nlm.nih.gov/pubmed/25737557 http://search.proquest.com/docview/1665573221 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4371922&tool=pmcentrez&rendertype=abstract GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 112 2015 11 3421-3426 |
| language |
English |
| source |
Enthalten in Proceedings of the National Academy of Sciences of the United States of America 112(2015), 11, Seite 3421-3426 volume:112 year:2015 number:11 pages:3421-3426 |
| sourceStr |
Enthalten in Proceedings of the National Academy of Sciences of the United States of America 112(2015), 11, Seite 3421-3426 volume:112 year:2015 number:11 pages:3421-3426 |
| format_phy_str_mv |
Article |
| institution |
findex.gbv.de |
| topic_facet |
Signal Transduction - radiation effects Gene Amplification - drug effects Glioma - enzymology Dacarbazine - therapeutic use Brain Neoplasms - enzymology Glioma - genetics DNA Repair - drug effects DNA Damage - genetics Isoenzymes - chemistry Drug Resistance, Neoplasm - drug effects DNA Repair - radiation effects Signal Transduction - drug effects Signal Transduction - genetics Radiation Tolerance - genetics Proto-Oncogene Proteins c-akt - chemistry Gene Amplification - radiation effects Isoenzymes - metabolism Brain Neoplasms - genetics Dacarbazine - pharmacology Proto-Oncogene Proteins c-akt - genetics DNA Repair - genetics Isoenzymes - genetics Brain Neoplasms - pathology Drug Resistance, Neoplasm - radiation effects Glioma - pathology Drug Resistance, Neoplasm - genetics Proto-Oncogene Proteins c-akt - metabolism Dacarbazine - analogs & derivatives Deoxyribonucleic acid--DNA Gene expression Tumors DNA repair Gene amplification Genomics glioma RCAS tv-a mouse model Biological Sciences Akt |
| dewey-raw |
500 |
| isfreeaccess_bool |
false |
| container_title |
Proceedings of the National Academy of Sciences of the United States of America |
| authorswithroles_txt_mv |
David E. Cogdell @@aut@@ Olli Yli-Harja @@oth@@ Matti Nykter @@oth@@ Youting Sun @@oth@@ Xinhui Zhou @@oth@@ Kristen M. Turner @@oth@@ W. K. Alfred Yung @@oth@@ Brady Bernard @@oth@@ Gregory N. Fuller @@oth@@ Ping Ji @@oth@@ Kirsi J. Granberg @@oth@@ Wei Zhang @@oth@@ Limei Hu @@oth@@ Ilya Shmulevich @@oth@@ |
| publishDateDaySort_date |
2015-01-01T00:00:00Z |
| hierarchy_top_id |
129505269 |
| dewey-sort |
3500 |
| id |
OLC1970258969 |
| language_de |
englisch |
| fullrecord |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a2200265 4500</leader><controlfield tag="001">OLC1970258969</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230714175846.0</controlfield><controlfield tag="007">tu</controlfield><controlfield tag="008">160211s2015 xx ||||| 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1073/pnas.1414573112</subfield><subfield code="2">doi</subfield></datafield><datafield tag="028" ind1="5" ind2="2"><subfield code="a">PQ20160211</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)OLC1970258969</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)GBVOLC1970258969</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(PRQ)c3056-414d47b6346f5ea0577f03f9d7ba8d02c0111186f8d2ab949b93165e369d71423</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(KEY)0583363920150000112001103421genomicallyamplifiedakt3activatesdnarepairpathwaya</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">500</subfield><subfield code="q">DNB</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">570</subfield><subfield code="q">AVZ</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">LING</subfield><subfield code="2">fid</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">BIODIV</subfield><subfield code="2">fid</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">David E. Cogdell</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Genomically amplified Akt3 activates DNA repair pathway and promotes glioma progression</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2015</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">ohne Hilfsmittel zu benutzen</subfield><subfield code="b">n</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Band</subfield><subfield code="b">nc</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Akt is a robust oncogene that plays key roles in the development and progression of many cancers, including glioma. We evaluated the differential propensities of the Akt isoforms toward progression in the well-characterized RCAS/Ntv-a mouse model of PDGFB-driven low grade glioma. A constitutively active myristoylated form of Akt1 did not induce high-grade glioma (HGG). In stark contrast, Akt2 and Akt3 showed strong progression potential with 78% and 97% of tumors diagnosed as HGG, respectively. We further revealed that significant variations in polarity and hydropathy values among the Akt isoforms in both the pleckstrin homology domain (P domain) and regulatory domain (R domain) were critical in mediating glioma progression. Gene expression profiles from representative Akt-derived tumors indicated dominant and distinct roles for Akt3, consisting primarily of DNA repair pathways. TCGA data from human GBM closely reflected the DNA repair function, as Akt3 was significantly correlated with a 76-gene signature DNA repair panel. Consistently, compared with Akt1 and Akt2 overexpression models, Akt3-expressing human GBM cells had enhanced activation of DNA repair proteins, leading to increased DNA repair and subsequent resistance to radiation and temozolomide. Given the wide range of Akt3-amplified cancers, Akt3 may represent a key resistance factor.</subfield></datafield><datafield tag="540" ind1=" " ind2=" "><subfield code="a">Nutzungsrecht: © COPYRIGHT 2015 National Academy of Sciences</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Signal Transduction - radiation effects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Gene Amplification - drug effects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Glioma - enzymology</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Dacarbazine - therapeutic use</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Brain Neoplasms - enzymology</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Glioma - genetics</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">DNA Repair - drug effects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">DNA Damage - genetics</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Isoenzymes - chemistry</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Drug Resistance, Neoplasm - drug effects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">DNA Repair - radiation effects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Signal Transduction - drug effects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Signal Transduction - genetics</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Radiation Tolerance - genetics</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Proto-Oncogene Proteins c-akt - chemistry</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Gene Amplification - radiation effects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Isoenzymes - metabolism</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Brain Neoplasms - genetics</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Dacarbazine - pharmacology</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Proto-Oncogene Proteins c-akt - genetics</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">DNA Repair - genetics</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Isoenzymes - genetics</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Brain Neoplasms - pathology</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Drug Resistance, Neoplasm - radiation effects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Glioma - pathology</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Drug Resistance, Neoplasm - genetics</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Proto-Oncogene Proteins c-akt - metabolism</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Dacarbazine - analogs & derivatives</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Deoxyribonucleic acid--DNA</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Gene expression</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Tumors</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">DNA repair</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Gene amplification</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Genomics</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">glioma</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">RCAS</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">tv-a mouse model</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Biological Sciences</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Akt</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Olli Yli-Harja</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Matti Nykter</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Youting Sun</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Xinhui Zhou</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Kristen M. Turner</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">W. K. Alfred Yung</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Brady Bernard</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Gregory N. Fuller</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Ping Ji</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Kirsi J. Granberg</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Wei Zhang</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Limei Hu</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Ilya Shmulevich</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Proceedings of the National Academy of Sciences of the United States of America</subfield><subfield code="d">Washington, DC : NAS, 1877</subfield><subfield code="g">112(2015), 11, Seite 3421-3426</subfield><subfield code="w">(DE-627)129505269</subfield><subfield code="w">(DE-600)209104-5</subfield><subfield code="w">(DE-576)014909189</subfield><subfield code="x">0027-8424</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:112</subfield><subfield code="g">year:2015</subfield><subfield code="g">number:11</subfield><subfield code="g">pages:3421-3426</subfield></datafield><datafield tag="856" ind1="4" ind2="1"><subfield code="u">http://dx.doi.org/10.1073/pnas.1414573112</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">http://www.pnas.org/content/112/11/3421.abstract</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">http://www.ncbi.nlm.nih.gov/pubmed/25737557</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">http://search.proquest.com/docview/1665573221</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4371922&tool=pmcentrez&rendertype=abstract</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_OLC</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">FID-LING</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">FID-BIODIV</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHY</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-CHE</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-MAT</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-FOR</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-DE-84</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OPC-MAT</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OPC-FOR</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_59</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">112</subfield><subfield code="j">2015</subfield><subfield code="e">11</subfield><subfield code="h">3421-3426</subfield></datafield></record></collection>
|
| author |
David E. Cogdell |
| spellingShingle |
David E. Cogdell ddc 500 ddc 570 fid LING fid BIODIV misc Signal Transduction - radiation effects misc Gene Amplification - drug effects misc Glioma - enzymology misc Dacarbazine - therapeutic use misc Brain Neoplasms - enzymology misc Glioma - genetics misc DNA Repair - drug effects misc DNA Damage - genetics misc Isoenzymes - chemistry misc Drug Resistance, Neoplasm - drug effects misc DNA Repair - radiation effects misc Signal Transduction - drug effects misc Signal Transduction - genetics misc Radiation Tolerance - genetics misc Proto-Oncogene Proteins c-akt - chemistry misc Gene Amplification - radiation effects misc Isoenzymes - metabolism misc Brain Neoplasms - genetics misc Dacarbazine - pharmacology misc Proto-Oncogene Proteins c-akt - genetics misc DNA Repair - genetics misc Isoenzymes - genetics misc Brain Neoplasms - pathology misc Drug Resistance, Neoplasm - radiation effects misc Glioma - pathology misc Drug Resistance, Neoplasm - genetics misc Proto-Oncogene Proteins c-akt - metabolism misc Dacarbazine - analogs & derivatives misc Deoxyribonucleic acid--DNA misc Gene expression misc Tumors misc DNA repair misc Gene amplification misc Genomics misc glioma misc RCAS misc tv-a mouse model misc Biological Sciences misc Akt Genomically amplified Akt3 activates DNA repair pathway and promotes glioma progression |
| authorStr |
David E. Cogdell |
| ppnlink_with_tag_str_mv |
@@773@@(DE-627)129505269 |
| format |
Article |
| dewey-ones |
500 - Natural sciences & mathematics 570 - Life sciences; biology |
| delete_txt_mv |
keep |
| author_role |
aut |
| collection |
OLC |
| remote_str |
false |
| illustrated |
Not Illustrated |
| issn |
0027-8424 |
| topic_title |
500 DNB 570 AVZ LING fid BIODIV fid Genomically amplified Akt3 activates DNA repair pathway and promotes glioma progression Signal Transduction - radiation effects Gene Amplification - drug effects Glioma - enzymology Dacarbazine - therapeutic use Brain Neoplasms - enzymology Glioma - genetics DNA Repair - drug effects DNA Damage - genetics Isoenzymes - chemistry Drug Resistance, Neoplasm - drug effects DNA Repair - radiation effects Signal Transduction - drug effects Signal Transduction - genetics Radiation Tolerance - genetics Proto-Oncogene Proteins c-akt - chemistry Gene Amplification - radiation effects Isoenzymes - metabolism Brain Neoplasms - genetics Dacarbazine - pharmacology Proto-Oncogene Proteins c-akt - genetics DNA Repair - genetics Isoenzymes - genetics Brain Neoplasms - pathology Drug Resistance, Neoplasm - radiation effects Glioma - pathology Drug Resistance, Neoplasm - genetics Proto-Oncogene Proteins c-akt - metabolism Dacarbazine - analogs & derivatives Deoxyribonucleic acid--DNA Gene expression Tumors DNA repair Gene amplification Genomics glioma RCAS tv-a mouse model Biological Sciences Akt |
| topic |
ddc 500 ddc 570 fid LING fid BIODIV misc Signal Transduction - radiation effects misc Gene Amplification - drug effects misc Glioma - enzymology misc Dacarbazine - therapeutic use misc Brain Neoplasms - enzymology misc Glioma - genetics misc DNA Repair - drug effects misc DNA Damage - genetics misc Isoenzymes - chemistry misc Drug Resistance, Neoplasm - drug effects misc DNA Repair - radiation effects misc Signal Transduction - drug effects misc Signal Transduction - genetics misc Radiation Tolerance - genetics misc Proto-Oncogene Proteins c-akt - chemistry misc Gene Amplification - radiation effects misc Isoenzymes - metabolism misc Brain Neoplasms - genetics misc Dacarbazine - pharmacology misc Proto-Oncogene Proteins c-akt - genetics misc DNA Repair - genetics misc Isoenzymes - genetics misc Brain Neoplasms - pathology misc Drug Resistance, Neoplasm - radiation effects misc Glioma - pathology misc Drug Resistance, Neoplasm - genetics misc Proto-Oncogene Proteins c-akt - metabolism misc Dacarbazine - analogs & derivatives misc Deoxyribonucleic acid--DNA misc Gene expression misc Tumors misc DNA repair misc Gene amplification misc Genomics misc glioma misc RCAS misc tv-a mouse model misc Biological Sciences misc Akt |
| topic_unstemmed |
ddc 500 ddc 570 fid LING fid BIODIV misc Signal Transduction - radiation effects misc Gene Amplification - drug effects misc Glioma - enzymology misc Dacarbazine - therapeutic use misc Brain Neoplasms - enzymology misc Glioma - genetics misc DNA Repair - drug effects misc DNA Damage - genetics misc Isoenzymes - chemistry misc Drug Resistance, Neoplasm - drug effects misc DNA Repair - radiation effects misc Signal Transduction - drug effects misc Signal Transduction - genetics misc Radiation Tolerance - genetics misc Proto-Oncogene Proteins c-akt - chemistry misc Gene Amplification - radiation effects misc Isoenzymes - metabolism misc Brain Neoplasms - genetics misc Dacarbazine - pharmacology misc Proto-Oncogene Proteins c-akt - genetics misc DNA Repair - genetics misc Isoenzymes - genetics misc Brain Neoplasms - pathology misc Drug Resistance, Neoplasm - radiation effects misc Glioma - pathology misc Drug Resistance, Neoplasm - genetics misc Proto-Oncogene Proteins c-akt - metabolism misc Dacarbazine - analogs & derivatives misc Deoxyribonucleic acid--DNA misc Gene expression misc Tumors misc DNA repair misc Gene amplification misc Genomics misc glioma misc RCAS misc tv-a mouse model misc Biological Sciences misc Akt |
| topic_browse |
ddc 500 ddc 570 fid LING fid BIODIV misc Signal Transduction - radiation effects misc Gene Amplification - drug effects misc Glioma - enzymology misc Dacarbazine - therapeutic use misc Brain Neoplasms - enzymology misc Glioma - genetics misc DNA Repair - drug effects misc DNA Damage - genetics misc Isoenzymes - chemistry misc Drug Resistance, Neoplasm - drug effects misc DNA Repair - radiation effects misc Signal Transduction - drug effects misc Signal Transduction - genetics misc Radiation Tolerance - genetics misc Proto-Oncogene Proteins c-akt - chemistry misc Gene Amplification - radiation effects misc Isoenzymes - metabolism misc Brain Neoplasms - genetics misc Dacarbazine - pharmacology misc Proto-Oncogene Proteins c-akt - genetics misc DNA Repair - genetics misc Isoenzymes - genetics misc Brain Neoplasms - pathology misc Drug Resistance, Neoplasm - radiation effects misc Glioma - pathology misc Drug Resistance, Neoplasm - genetics misc Proto-Oncogene Proteins c-akt - metabolism misc Dacarbazine - analogs & derivatives misc Deoxyribonucleic acid--DNA misc Gene expression misc Tumors misc DNA repair misc Gene amplification misc Genomics misc glioma misc RCAS misc tv-a mouse model misc Biological Sciences misc Akt |
| format_facet |
Aufsätze Gedruckte Aufsätze |
| format_main_str_mv |
Text Zeitschrift/Artikel |
| carriertype_str_mv |
nc |
| author2_variant |
o y h oyh m n mn y s ys x z xz k m t kmt w k a y wkay b b bb g n f gnf p j pj k j g kjg w z wz l h lh i s is |
| hierarchy_parent_title |
Proceedings of the National Academy of Sciences of the United States of America |
| hierarchy_parent_id |
129505269 |
| dewey-tens |
500 - Science 570 - Life sciences; biology |
| hierarchy_top_title |
Proceedings of the National Academy of Sciences of the United States of America |
| isfreeaccess_txt |
false |
| familylinks_str_mv |
(DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 |
| title |
Genomically amplified Akt3 activates DNA repair pathway and promotes glioma progression |
| ctrlnum |
(DE-627)OLC1970258969 (DE-599)GBVOLC1970258969 (PRQ)c3056-414d47b6346f5ea0577f03f9d7ba8d02c0111186f8d2ab949b93165e369d71423 (KEY)0583363920150000112001103421genomicallyamplifiedakt3activatesdnarepairpathwaya |
| title_full |
Genomically amplified Akt3 activates DNA repair pathway and promotes glioma progression |
| author_sort |
David E. Cogdell |
| journal |
Proceedings of the National Academy of Sciences of the United States of America |
| journalStr |
Proceedings of the National Academy of Sciences of the United States of America |
| lang_code |
eng |
| isOA_bool |
false |
| dewey-hundreds |
500 - Science |
| recordtype |
marc |
| publishDateSort |
2015 |
| contenttype_str_mv |
txt |
| container_start_page |
3421 |
| author_browse |
David E. Cogdell |
| container_volume |
112 |
| class |
500 DNB 570 AVZ LING fid BIODIV fid |
| format_se |
Aufsätze |
| author-letter |
David E. Cogdell |
| doi_str_mv |
10.1073/pnas.1414573112 |
| dewey-full |
500 570 |
| title_sort |
genomically amplified akt3 activates dna repair pathway and promotes glioma progression |
| title_auth |
Genomically amplified Akt3 activates DNA repair pathway and promotes glioma progression |
| abstract |
Akt is a robust oncogene that plays key roles in the development and progression of many cancers, including glioma. We evaluated the differential propensities of the Akt isoforms toward progression in the well-characterized RCAS/Ntv-a mouse model of PDGFB-driven low grade glioma. A constitutively active myristoylated form of Akt1 did not induce high-grade glioma (HGG). In stark contrast, Akt2 and Akt3 showed strong progression potential with 78% and 97% of tumors diagnosed as HGG, respectively. We further revealed that significant variations in polarity and hydropathy values among the Akt isoforms in both the pleckstrin homology domain (P domain) and regulatory domain (R domain) were critical in mediating glioma progression. Gene expression profiles from representative Akt-derived tumors indicated dominant and distinct roles for Akt3, consisting primarily of DNA repair pathways. TCGA data from human GBM closely reflected the DNA repair function, as Akt3 was significantly correlated with a 76-gene signature DNA repair panel. Consistently, compared with Akt1 and Akt2 overexpression models, Akt3-expressing human GBM cells had enhanced activation of DNA repair proteins, leading to increased DNA repair and subsequent resistance to radiation and temozolomide. Given the wide range of Akt3-amplified cancers, Akt3 may represent a key resistance factor. |
| abstractGer |
Akt is a robust oncogene that plays key roles in the development and progression of many cancers, including glioma. We evaluated the differential propensities of the Akt isoforms toward progression in the well-characterized RCAS/Ntv-a mouse model of PDGFB-driven low grade glioma. A constitutively active myristoylated form of Akt1 did not induce high-grade glioma (HGG). In stark contrast, Akt2 and Akt3 showed strong progression potential with 78% and 97% of tumors diagnosed as HGG, respectively. We further revealed that significant variations in polarity and hydropathy values among the Akt isoforms in both the pleckstrin homology domain (P domain) and regulatory domain (R domain) were critical in mediating glioma progression. Gene expression profiles from representative Akt-derived tumors indicated dominant and distinct roles for Akt3, consisting primarily of DNA repair pathways. TCGA data from human GBM closely reflected the DNA repair function, as Akt3 was significantly correlated with a 76-gene signature DNA repair panel. Consistently, compared with Akt1 and Akt2 overexpression models, Akt3-expressing human GBM cells had enhanced activation of DNA repair proteins, leading to increased DNA repair and subsequent resistance to radiation and temozolomide. Given the wide range of Akt3-amplified cancers, Akt3 may represent a key resistance factor. |
| abstract_unstemmed |
Akt is a robust oncogene that plays key roles in the development and progression of many cancers, including glioma. We evaluated the differential propensities of the Akt isoforms toward progression in the well-characterized RCAS/Ntv-a mouse model of PDGFB-driven low grade glioma. A constitutively active myristoylated form of Akt1 did not induce high-grade glioma (HGG). In stark contrast, Akt2 and Akt3 showed strong progression potential with 78% and 97% of tumors diagnosed as HGG, respectively. We further revealed that significant variations in polarity and hydropathy values among the Akt isoforms in both the pleckstrin homology domain (P domain) and regulatory domain (R domain) were critical in mediating glioma progression. Gene expression profiles from representative Akt-derived tumors indicated dominant and distinct roles for Akt3, consisting primarily of DNA repair pathways. TCGA data from human GBM closely reflected the DNA repair function, as Akt3 was significantly correlated with a 76-gene signature DNA repair panel. Consistently, compared with Akt1 and Akt2 overexpression models, Akt3-expressing human GBM cells had enhanced activation of DNA repair proteins, leading to increased DNA repair and subsequent resistance to radiation and temozolomide. Given the wide range of Akt3-amplified cancers, Akt3 may represent a key resistance factor. |
| collection_details |
GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 |
| container_issue |
11 |
| title_short |
Genomically amplified Akt3 activates DNA repair pathway and promotes glioma progression |
| url |
http://dx.doi.org/10.1073/pnas.1414573112 http://www.pnas.org/content/112/11/3421.abstract http://www.ncbi.nlm.nih.gov/pubmed/25737557 http://search.proquest.com/docview/1665573221 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4371922&tool=pmcentrez&rendertype=abstract |
| remote_bool |
false |
| author2 |
Olli Yli-Harja Matti Nykter Youting Sun Xinhui Zhou Kristen M. Turner W. K. Alfred Yung Brady Bernard Gregory N. Fuller Ping Ji Kirsi J. Granberg Wei Zhang Limei Hu Ilya Shmulevich |
| author2Str |
Olli Yli-Harja Matti Nykter Youting Sun Xinhui Zhou Kristen M. Turner W. K. Alfred Yung Brady Bernard Gregory N. Fuller Ping Ji Kirsi J. Granberg Wei Zhang Limei Hu Ilya Shmulevich |
| ppnlink |
129505269 |
| mediatype_str_mv |
n |
| isOA_txt |
false |
| hochschulschrift_bool |
false |
| author2_role |
oth oth oth oth oth oth oth oth oth oth oth oth oth |
| doi_str |
10.1073/pnas.1414573112 |
| up_date |
2024-07-03T14:29:36.651Z |
| _version_ |
1803568521310896128 |
| fullrecord_marcxml |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a2200265 4500</leader><controlfield tag="001">OLC1970258969</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230714175846.0</controlfield><controlfield tag="007">tu</controlfield><controlfield tag="008">160211s2015 xx ||||| 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1073/pnas.1414573112</subfield><subfield code="2">doi</subfield></datafield><datafield tag="028" ind1="5" ind2="2"><subfield code="a">PQ20160211</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)OLC1970258969</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)GBVOLC1970258969</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(PRQ)c3056-414d47b6346f5ea0577f03f9d7ba8d02c0111186f8d2ab949b93165e369d71423</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(KEY)0583363920150000112001103421genomicallyamplifiedakt3activatesdnarepairpathwaya</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">500</subfield><subfield code="q">DNB</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">570</subfield><subfield code="q">AVZ</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">LING</subfield><subfield code="2">fid</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">BIODIV</subfield><subfield code="2">fid</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">David E. Cogdell</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Genomically amplified Akt3 activates DNA repair pathway and promotes glioma progression</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2015</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">ohne Hilfsmittel zu benutzen</subfield><subfield code="b">n</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Band</subfield><subfield code="b">nc</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Akt is a robust oncogene that plays key roles in the development and progression of many cancers, including glioma. We evaluated the differential propensities of the Akt isoforms toward progression in the well-characterized RCAS/Ntv-a mouse model of PDGFB-driven low grade glioma. A constitutively active myristoylated form of Akt1 did not induce high-grade glioma (HGG). In stark contrast, Akt2 and Akt3 showed strong progression potential with 78% and 97% of tumors diagnosed as HGG, respectively. We further revealed that significant variations in polarity and hydropathy values among the Akt isoforms in both the pleckstrin homology domain (P domain) and regulatory domain (R domain) were critical in mediating glioma progression. Gene expression profiles from representative Akt-derived tumors indicated dominant and distinct roles for Akt3, consisting primarily of DNA repair pathways. TCGA data from human GBM closely reflected the DNA repair function, as Akt3 was significantly correlated with a 76-gene signature DNA repair panel. Consistently, compared with Akt1 and Akt2 overexpression models, Akt3-expressing human GBM cells had enhanced activation of DNA repair proteins, leading to increased DNA repair and subsequent resistance to radiation and temozolomide. Given the wide range of Akt3-amplified cancers, Akt3 may represent a key resistance factor.</subfield></datafield><datafield tag="540" ind1=" " ind2=" "><subfield code="a">Nutzungsrecht: © COPYRIGHT 2015 National Academy of Sciences</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Signal Transduction - radiation effects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Gene Amplification - drug effects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Glioma - enzymology</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Dacarbazine - therapeutic use</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Brain Neoplasms - enzymology</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Glioma - genetics</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">DNA Repair - drug effects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">DNA Damage - genetics</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Isoenzymes - chemistry</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Drug Resistance, Neoplasm - drug effects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">DNA Repair - radiation effects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Signal Transduction - drug effects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Signal Transduction - genetics</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Radiation Tolerance - genetics</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Proto-Oncogene Proteins c-akt - chemistry</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Gene Amplification - radiation effects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Isoenzymes - metabolism</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Brain Neoplasms - genetics</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Dacarbazine - pharmacology</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Proto-Oncogene Proteins c-akt - genetics</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">DNA Repair - genetics</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Isoenzymes - genetics</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Brain Neoplasms - pathology</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Drug Resistance, Neoplasm - radiation effects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Glioma - pathology</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Drug Resistance, Neoplasm - genetics</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Proto-Oncogene Proteins c-akt - metabolism</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Dacarbazine - analogs & derivatives</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Deoxyribonucleic acid--DNA</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Gene expression</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Tumors</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">DNA repair</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Gene amplification</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Genomics</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">glioma</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">RCAS</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">tv-a mouse model</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Biological Sciences</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Akt</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Olli Yli-Harja</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Matti Nykter</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Youting Sun</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Xinhui Zhou</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Kristen M. Turner</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">W. K. Alfred Yung</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Brady Bernard</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Gregory N. Fuller</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Ping Ji</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Kirsi J. Granberg</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Wei Zhang</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Limei Hu</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Ilya Shmulevich</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Proceedings of the National Academy of Sciences of the United States of America</subfield><subfield code="d">Washington, DC : NAS, 1877</subfield><subfield code="g">112(2015), 11, Seite 3421-3426</subfield><subfield code="w">(DE-627)129505269</subfield><subfield code="w">(DE-600)209104-5</subfield><subfield code="w">(DE-576)014909189</subfield><subfield code="x">0027-8424</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:112</subfield><subfield code="g">year:2015</subfield><subfield code="g">number:11</subfield><subfield code="g">pages:3421-3426</subfield></datafield><datafield tag="856" ind1="4" ind2="1"><subfield code="u">http://dx.doi.org/10.1073/pnas.1414573112</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">http://www.pnas.org/content/112/11/3421.abstract</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">http://www.ncbi.nlm.nih.gov/pubmed/25737557</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">http://search.proquest.com/docview/1665573221</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4371922&tool=pmcentrez&rendertype=abstract</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_OLC</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">FID-LING</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">FID-BIODIV</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHY</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-CHE</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-MAT</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-FOR</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-DE-84</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OPC-MAT</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OPC-FOR</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_59</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">112</subfield><subfield code="j">2015</subfield><subfield code="e">11</subfield><subfield code="h">3421-3426</subfield></datafield></record></collection>
|
| score |
7.399581 |