Alternative to the soft-agar assay that permits high-throughput drug and genetic screens for cellular transformation
Colony formation in soft agar is the gold-standard assay for cellular transformation in vitro, but it is unsuited for high-throughput screening. Here, we describe an assay for cellular transformation that involves growth in low attachment (GILA) conditions and is strongly correlated with the soft-ag...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
John G. Doench [verfasserIn] |
|---|
| Format: |
Artikel |
|---|---|
| Sprache: |
Englisch |
| Erschienen: |
2015 |
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| Rechteinformationen: |
Nutzungsrecht: © COPYRIGHT 2015 National Academy of Sciences |
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| Schlagwörter: |
Breast Neoplasms - drug therapy Ovarian Neoplasms - drug therapy Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology |
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| Übergeordnetes Werk: |
Enthalten in: Proceedings of the National Academy of Sciences of the United States of America - Washington, DC : NAS, 1877, 112(2015), 18, Seite 5708-5713 |
|---|---|
| Übergeordnetes Werk: |
volume:112 ; year:2015 ; number:18 ; pages:5708-5713 |
| Links: |
|---|
| DOI / URN: |
10.1073/pnas.1505979112 |
|---|
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| 520 | |a Colony formation in soft agar is the gold-standard assay for cellular transformation in vitro, but it is unsuited for high-throughput screening. Here, we describe an assay for cellular transformation that involves growth in low attachment (GILA) conditions and is strongly correlated with the soft-agar assay. Using GILA, we describe high-throughput screens for drugs and genes that selectively inhibit or increase transformation, but not proliferation. Such molecules are unlikely to be found through conventional drug screening, and they include kinase inhibitors and drugs for noncancer diseases. In addition to known oncogenes, the genetic screen identifies genes that contribute to cellular transformation. Lastly, we demonstrate the ability of Food and Drug Administration-approved noncancer drugs to selectively kill ovarian cancer cells derived from patients with chemotherapy-resistant disease, suggesting this approach may provide useful information for personalized cancer treatment. | ||
| 540 | |a Nutzungsrecht: © COPYRIGHT 2015 National Academy of Sciences | ||
| 650 | 4 | |a Breast Neoplasms - drug therapy | |
| 650 | 4 | |a Ovarian Neoplasms - drug therapy | |
| 650 | 4 | |a Antineoplastic Agents - chemistry | |
| 650 | 4 | |a Antineoplastic Agents - pharmacology | |
| 650 | 4 | |a Ovarian Neoplasms - pathology | |
| 650 | 4 | |a Breast Neoplasms - pathology | |
| 650 | 4 | |a Adenosine Triphosphate - chemistry | |
| 650 | 4 | |a Fibroblasts - pathology | |
| 650 | 4 | |a Agar - chemistry | |
| 650 | 4 | |a Genetic screening | |
| 650 | 4 | |a Observations | |
| 650 | 4 | |a Biological assay | |
| 650 | 4 | |a Genetic transformation | |
| 650 | 4 | |a Methods | |
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| 700 | 0 | |a Levi A. Garraway |4 oth | |
| 700 | 0 | |a Zhe Ji |4 oth | |
| 700 | 0 | |a Andreas Janzer |4 oth | |
| 700 | 0 | |a Kevin Struhl |4 oth | |
| 700 | 0 | |a Benjamin Izar |4 oth | |
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10.1073/pnas.1505979112 doi PQ20160211 (DE-627)OLC1970267755 (DE-599)GBVOLC1970267755 (PRQ)c2505-1d13cbb95beb98c996bbe6c599cd426cecc21445aa61177d5087213bafef3f043 (KEY)0583363920150000112001805708alternativetothesoftagarassaythatpermitshighthroug DE-627 ger DE-627 rakwb eng 500 DNB 570 AVZ LING fid BIODIV fid John G. Doench verfasserin aut Alternative to the soft-agar assay that permits high-throughput drug and genetic screens for cellular transformation 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Colony formation in soft agar is the gold-standard assay for cellular transformation in vitro, but it is unsuited for high-throughput screening. Here, we describe an assay for cellular transformation that involves growth in low attachment (GILA) conditions and is strongly correlated with the soft-agar assay. Using GILA, we describe high-throughput screens for drugs and genes that selectively inhibit or increase transformation, but not proliferation. Such molecules are unlikely to be found through conventional drug screening, and they include kinase inhibitors and drugs for noncancer diseases. In addition to known oncogenes, the genetic screen identifies genes that contribute to cellular transformation. Lastly, we demonstrate the ability of Food and Drug Administration-approved noncancer drugs to selectively kill ovarian cancer cells derived from patients with chemotherapy-resistant disease, suggesting this approach may provide useful information for personalized cancer treatment. Nutzungsrecht: © COPYRIGHT 2015 National Academy of Sciences Breast Neoplasms - drug therapy Ovarian Neoplasms - drug therapy Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Ovarian Neoplasms - pathology Breast Neoplasms - pathology Adenosine Triphosphate - chemistry Fibroblasts - pathology Agar - chemistry Genetic screening Observations Biological assay Genetic transformation Methods Kinases Genetics Molecules Correlation analysis Biological assays Algae Asaf Rotem oth Levi A. Garraway oth Zhe Ji oth Andreas Janzer oth Kevin Struhl oth Benjamin Izar oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 112(2015), 18, Seite 5708-5713 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:112 year:2015 number:18 pages:5708-5713 http://dx.doi.org/10.1073/pnas.1505979112 Volltext http://www.pnas.org/content/112/18/5708.abstract http://www.ncbi.nlm.nih.gov/pubmed/25902495 http://search.proquest.com/docview/1682906931 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 18 5708-5713 |
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alternative to the soft-agar assay that permits high-throughput drug and genetic screens for cellular transformation |
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Alternative to the soft-agar assay that permits high-throughput drug and genetic screens for cellular transformation |
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Colony formation in soft agar is the gold-standard assay for cellular transformation in vitro, but it is unsuited for high-throughput screening. Here, we describe an assay for cellular transformation that involves growth in low attachment (GILA) conditions and is strongly correlated with the soft-agar assay. Using GILA, we describe high-throughput screens for drugs and genes that selectively inhibit or increase transformation, but not proliferation. Such molecules are unlikely to be found through conventional drug screening, and they include kinase inhibitors and drugs for noncancer diseases. In addition to known oncogenes, the genetic screen identifies genes that contribute to cellular transformation. Lastly, we demonstrate the ability of Food and Drug Administration-approved noncancer drugs to selectively kill ovarian cancer cells derived from patients with chemotherapy-resistant disease, suggesting this approach may provide useful information for personalized cancer treatment. |
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Colony formation in soft agar is the gold-standard assay for cellular transformation in vitro, but it is unsuited for high-throughput screening. Here, we describe an assay for cellular transformation that involves growth in low attachment (GILA) conditions and is strongly correlated with the soft-agar assay. Using GILA, we describe high-throughput screens for drugs and genes that selectively inhibit or increase transformation, but not proliferation. Such molecules are unlikely to be found through conventional drug screening, and they include kinase inhibitors and drugs for noncancer diseases. In addition to known oncogenes, the genetic screen identifies genes that contribute to cellular transformation. Lastly, we demonstrate the ability of Food and Drug Administration-approved noncancer drugs to selectively kill ovarian cancer cells derived from patients with chemotherapy-resistant disease, suggesting this approach may provide useful information for personalized cancer treatment. |
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Colony formation in soft agar is the gold-standard assay for cellular transformation in vitro, but it is unsuited for high-throughput screening. Here, we describe an assay for cellular transformation that involves growth in low attachment (GILA) conditions and is strongly correlated with the soft-agar assay. Using GILA, we describe high-throughput screens for drugs and genes that selectively inhibit or increase transformation, but not proliferation. Such molecules are unlikely to be found through conventional drug screening, and they include kinase inhibitors and drugs for noncancer diseases. In addition to known oncogenes, the genetic screen identifies genes that contribute to cellular transformation. Lastly, we demonstrate the ability of Food and Drug Administration-approved noncancer drugs to selectively kill ovarian cancer cells derived from patients with chemotherapy-resistant disease, suggesting this approach may provide useful information for personalized cancer treatment. |
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Alternative to the soft-agar assay that permits high-throughput drug and genetic screens for cellular transformation |
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Here, we describe an assay for cellular transformation that involves growth in low attachment (GILA) conditions and is strongly correlated with the soft-agar assay. Using GILA, we describe high-throughput screens for drugs and genes that selectively inhibit or increase transformation, but not proliferation. Such molecules are unlikely to be found through conventional drug screening, and they include kinase inhibitors and drugs for noncancer diseases. In addition to known oncogenes, the genetic screen identifies genes that contribute to cellular transformation. 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Garraway</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Zhe Ji</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Andreas Janzer</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Kevin Struhl</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Benjamin Izar</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), 18, Seite 5708-5713</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:18</subfield><subfield code="g">pages:5708-5713</subfield></datafield><datafield tag="856" ind1="4" ind2="1"><subfield code="u">http://dx.doi.org/10.1073/pnas.1505979112</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">http://www.pnas.org/content/112/18/5708.abstract</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">http://www.ncbi.nlm.nih.gov/pubmed/25902495</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">http://search.proquest.com/docview/1682906931</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">18</subfield><subfield code="h">5708-5713</subfield></datafield></record></collection>
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