Akt Regulated Phosphorylation of GSK-3β/Cyclin D1, p21 and p27 Contributes to Cell Proliferation Through Cell Cycle Progression From G1 to S/G2M Phase in Low-Dose Arsenite Exposed HaCat Cells

Arsenic is a toxic environmental contaminant. Long-term exposure to arsenic through drinking water induces human cancers. However, it is as yet uncertain about the mechanisms of arsenic induced carcinogenesis. Although the effects of low-dose arsenicals on proliferation and cell cycle have been reve...
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Autor*in:	Yao Chen [verfasserIn] Xudan Liu [verfasserIn] Huanhuan Wang [verfasserIn] Shiyi Liu [verfasserIn] Nannan Hu [verfasserIn] Xin Li [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	arsenite Akt p-GSK-3β p-cyclin D1 p-p21 p-p27

Übergeordnetes Werk:	In: Frontiers in Pharmacology - Frontiers Media S.A., 2010, 10(2019)
Übergeordnetes Werk:	volume:10 ; year:2019

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fphar.2019.01176

Katalog-ID:	DOAJ045952655

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spelling	10.3389/fphar.2019.01176 doi (DE-627)DOAJ045952655 (DE-599)DOAJdd0dfc8beb4840bca2b815f62302eeb1 DE-627 ger DE-627 rakwb eng RM1-950 Yao Chen verfasserin aut Akt Regulated Phosphorylation of GSK-3β/Cyclin D1, p21 and p27 Contributes to Cell Proliferation Through Cell Cycle Progression From G1 to S/G2M Phase in Low-Dose Arsenite Exposed HaCat Cells 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Arsenic is a toxic environmental contaminant. Long-term exposure to arsenic through drinking water induces human cancers. However, it is as yet uncertain about the mechanisms of arsenic induced carcinogenesis. Although the effects of low-dose arsenicals on proliferation and cell cycle have been revealed by short time exposure, the evidences for long-term exposure were seldom reported. The detailed mechanism has been unclear and supplemented constantly. In the present study, we used normal human keratinocytes (HaCat) to study the effects of long-term, low-dose sodium arsenite (NaAsO2) exposure on cell proliferation with emphasis on the Akt regulated cell cycle signaling pathways. Treatment of NaAsO2 resulted in increased cell proliferation and promotion of cell cycle progression from G1 to S/G2M phase, both of which could be attenuated by MK2206, a highly selective inhibitor of Akt. Along with the increased expression of phospho-Akt (p-Akt, Ser 473), increased expression of p-GSK-3β (Ser 9), p-p21 (Thr 145), p-p27 (Thr 157) and total cyclin D1, and decreased expression of p-cyclin D1 (Thr 286), p21 and p27 were also found in the NaAsO2 exposed cells. Treatment of MK2206 markedly reversed the expression of all of the above proteins. Our findings indicated that the phosphorylated activation of Akt played a role in the proliferation of HaCat cells upon long-term, low-dose NaAsO2 exposure through the phosphorylative regulation of its downstream cell cycle regulating factors of GSK-3β/cyclin D1, p21 and p27, which could induce the promotion of cell cycle progression from G1 to S/G2M phase. arsenite Akt p-GSK-3β p-cyclin D1 p-p21 p-p27 Therapeutics. Pharmacology Xudan Liu verfasserin aut Huanhuan Wang verfasserin aut Shiyi Liu verfasserin aut Nannan Hu verfasserin aut Xin Li verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 10(2019) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:10 year:2019 https://doi.org/10.3389/fphar.2019.01176 kostenfrei https://doaj.org/article/dd0dfc8beb4840bca2b815f62302eeb1 kostenfrei https://www.frontiersin.org/article/10.3389/fphar.2019.01176/full kostenfrei https://doaj.org/toc/1663-9812 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2019
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allfieldsGer	10.3389/fphar.2019.01176 doi (DE-627)DOAJ045952655 (DE-599)DOAJdd0dfc8beb4840bca2b815f62302eeb1 DE-627 ger DE-627 rakwb eng RM1-950 Yao Chen verfasserin aut Akt Regulated Phosphorylation of GSK-3β/Cyclin D1, p21 and p27 Contributes to Cell Proliferation Through Cell Cycle Progression From G1 to S/G2M Phase in Low-Dose Arsenite Exposed HaCat Cells 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Arsenic is a toxic environmental contaminant. Long-term exposure to arsenic through drinking water induces human cancers. However, it is as yet uncertain about the mechanisms of arsenic induced carcinogenesis. Although the effects of low-dose arsenicals on proliferation and cell cycle have been revealed by short time exposure, the evidences for long-term exposure were seldom reported. The detailed mechanism has been unclear and supplemented constantly. In the present study, we used normal human keratinocytes (HaCat) to study the effects of long-term, low-dose sodium arsenite (NaAsO2) exposure on cell proliferation with emphasis on the Akt regulated cell cycle signaling pathways. Treatment of NaAsO2 resulted in increased cell proliferation and promotion of cell cycle progression from G1 to S/G2M phase, both of which could be attenuated by MK2206, a highly selective inhibitor of Akt. Along with the increased expression of phospho-Akt (p-Akt, Ser 473), increased expression of p-GSK-3β (Ser 9), p-p21 (Thr 145), p-p27 (Thr 157) and total cyclin D1, and decreased expression of p-cyclin D1 (Thr 286), p21 and p27 were also found in the NaAsO2 exposed cells. Treatment of MK2206 markedly reversed the expression of all of the above proteins. Our findings indicated that the phosphorylated activation of Akt played a role in the proliferation of HaCat cells upon long-term, low-dose NaAsO2 exposure through the phosphorylative regulation of its downstream cell cycle regulating factors of GSK-3β/cyclin D1, p21 and p27, which could induce the promotion of cell cycle progression from G1 to S/G2M phase. arsenite Akt p-GSK-3β p-cyclin D1 p-p21 p-p27 Therapeutics. Pharmacology Xudan Liu verfasserin aut Huanhuan Wang verfasserin aut Shiyi Liu verfasserin aut Nannan Hu verfasserin aut Xin Li verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 10(2019) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:10 year:2019 https://doi.org/10.3389/fphar.2019.01176 kostenfrei https://doaj.org/article/dd0dfc8beb4840bca2b815f62302eeb1 kostenfrei https://www.frontiersin.org/article/10.3389/fphar.2019.01176/full kostenfrei https://doaj.org/toc/1663-9812 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2019
allfieldsSound	10.3389/fphar.2019.01176 doi (DE-627)DOAJ045952655 (DE-599)DOAJdd0dfc8beb4840bca2b815f62302eeb1 DE-627 ger DE-627 rakwb eng RM1-950 Yao Chen verfasserin aut Akt Regulated Phosphorylation of GSK-3β/Cyclin D1, p21 and p27 Contributes to Cell Proliferation Through Cell Cycle Progression From G1 to S/G2M Phase in Low-Dose Arsenite Exposed HaCat Cells 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Arsenic is a toxic environmental contaminant. Long-term exposure to arsenic through drinking water induces human cancers. However, it is as yet uncertain about the mechanisms of arsenic induced carcinogenesis. Although the effects of low-dose arsenicals on proliferation and cell cycle have been revealed by short time exposure, the evidences for long-term exposure were seldom reported. The detailed mechanism has been unclear and supplemented constantly. In the present study, we used normal human keratinocytes (HaCat) to study the effects of long-term, low-dose sodium arsenite (NaAsO2) exposure on cell proliferation with emphasis on the Akt regulated cell cycle signaling pathways. Treatment of NaAsO2 resulted in increased cell proliferation and promotion of cell cycle progression from G1 to S/G2M phase, both of which could be attenuated by MK2206, a highly selective inhibitor of Akt. Along with the increased expression of phospho-Akt (p-Akt, Ser 473), increased expression of p-GSK-3β (Ser 9), p-p21 (Thr 145), p-p27 (Thr 157) and total cyclin D1, and decreased expression of p-cyclin D1 (Thr 286), p21 and p27 were also found in the NaAsO2 exposed cells. Treatment of MK2206 markedly reversed the expression of all of the above proteins. Our findings indicated that the phosphorylated activation of Akt played a role in the proliferation of HaCat cells upon long-term, low-dose NaAsO2 exposure through the phosphorylative regulation of its downstream cell cycle regulating factors of GSK-3β/cyclin D1, p21 and p27, which could induce the promotion of cell cycle progression from G1 to S/G2M phase. arsenite Akt p-GSK-3β p-cyclin D1 p-p21 p-p27 Therapeutics. Pharmacology Xudan Liu verfasserin aut Huanhuan Wang verfasserin aut Shiyi Liu verfasserin aut Nannan Hu verfasserin aut Xin Li verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 10(2019) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:10 year:2019 https://doi.org/10.3389/fphar.2019.01176 kostenfrei https://doaj.org/article/dd0dfc8beb4840bca2b815f62302eeb1 kostenfrei https://www.frontiersin.org/article/10.3389/fphar.2019.01176/full kostenfrei https://doaj.org/toc/1663-9812 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2019
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authorswithroles_txt_mv	Yao Chen @@aut@@ Xudan Liu @@aut@@ Huanhuan Wang @@aut@@ Shiyi Liu @@aut@@ Nannan Hu @@aut@@ Xin Li @@aut@@
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callnumber-first	R - Medicine
author	Yao Chen
spellingShingle	Yao Chen misc RM1-950 misc arsenite misc Akt misc p-GSK-3β misc p-cyclin D1 misc p-p21 misc p-p27 misc Therapeutics. Pharmacology Akt Regulated Phosphorylation of GSK-3β/Cyclin D1, p21 and p27 Contributes to Cell Proliferation Through Cell Cycle Progression From G1 to S/G2M Phase in Low-Dose Arsenite Exposed HaCat Cells
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topic_title	RM1-950 Akt Regulated Phosphorylation of GSK-3β/Cyclin D1, p21 and p27 Contributes to Cell Proliferation Through Cell Cycle Progression From G1 to S/G2M Phase in Low-Dose Arsenite Exposed HaCat Cells arsenite Akt p-GSK-3β p-cyclin D1 p-p21 p-p27
topic	misc RM1-950 misc arsenite misc Akt misc p-GSK-3β misc p-cyclin D1 misc p-p21 misc p-p27 misc Therapeutics. Pharmacology
topic_unstemmed	misc RM1-950 misc arsenite misc Akt misc p-GSK-3β misc p-cyclin D1 misc p-p21 misc p-p27 misc Therapeutics. Pharmacology
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title	Akt Regulated Phosphorylation of GSK-3β/Cyclin D1, p21 and p27 Contributes to Cell Proliferation Through Cell Cycle Progression From G1 to S/G2M Phase in Low-Dose Arsenite Exposed HaCat Cells
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title_full	Akt Regulated Phosphorylation of GSK-3β/Cyclin D1, p21 and p27 Contributes to Cell Proliferation Through Cell Cycle Progression From G1 to S/G2M Phase in Low-Dose Arsenite Exposed HaCat Cells
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title_sort	akt regulated phosphorylation of gsk-3β/cyclin d1, p21 and p27 contributes to cell proliferation through cell cycle progression from g1 to s/g2m phase in low-dose arsenite exposed hacat cells
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title_auth	Akt Regulated Phosphorylation of GSK-3β/Cyclin D1, p21 and p27 Contributes to Cell Proliferation Through Cell Cycle Progression From G1 to S/G2M Phase in Low-Dose Arsenite Exposed HaCat Cells
abstract	Arsenic is a toxic environmental contaminant. Long-term exposure to arsenic through drinking water induces human cancers. However, it is as yet uncertain about the mechanisms of arsenic induced carcinogenesis. Although the effects of low-dose arsenicals on proliferation and cell cycle have been revealed by short time exposure, the evidences for long-term exposure were seldom reported. The detailed mechanism has been unclear and supplemented constantly. In the present study, we used normal human keratinocytes (HaCat) to study the effects of long-term, low-dose sodium arsenite (NaAsO2) exposure on cell proliferation with emphasis on the Akt regulated cell cycle signaling pathways. Treatment of NaAsO2 resulted in increased cell proliferation and promotion of cell cycle progression from G1 to S/G2M phase, both of which could be attenuated by MK2206, a highly selective inhibitor of Akt. Along with the increased expression of phospho-Akt (p-Akt, Ser 473), increased expression of p-GSK-3β (Ser 9), p-p21 (Thr 145), p-p27 (Thr 157) and total cyclin D1, and decreased expression of p-cyclin D1 (Thr 286), p21 and p27 were also found in the NaAsO2 exposed cells. Treatment of MK2206 markedly reversed the expression of all of the above proteins. Our findings indicated that the phosphorylated activation of Akt played a role in the proliferation of HaCat cells upon long-term, low-dose NaAsO2 exposure through the phosphorylative regulation of its downstream cell cycle regulating factors of GSK-3β/cyclin D1, p21 and p27, which could induce the promotion of cell cycle progression from G1 to S/G2M phase.
abstractGer	Arsenic is a toxic environmental contaminant. Long-term exposure to arsenic through drinking water induces human cancers. However, it is as yet uncertain about the mechanisms of arsenic induced carcinogenesis. Although the effects of low-dose arsenicals on proliferation and cell cycle have been revealed by short time exposure, the evidences for long-term exposure were seldom reported. The detailed mechanism has been unclear and supplemented constantly. In the present study, we used normal human keratinocytes (HaCat) to study the effects of long-term, low-dose sodium arsenite (NaAsO2) exposure on cell proliferation with emphasis on the Akt regulated cell cycle signaling pathways. Treatment of NaAsO2 resulted in increased cell proliferation and promotion of cell cycle progression from G1 to S/G2M phase, both of which could be attenuated by MK2206, a highly selective inhibitor of Akt. Along with the increased expression of phospho-Akt (p-Akt, Ser 473), increased expression of p-GSK-3β (Ser 9), p-p21 (Thr 145), p-p27 (Thr 157) and total cyclin D1, and decreased expression of p-cyclin D1 (Thr 286), p21 and p27 were also found in the NaAsO2 exposed cells. Treatment of MK2206 markedly reversed the expression of all of the above proteins. Our findings indicated that the phosphorylated activation of Akt played a role in the proliferation of HaCat cells upon long-term, low-dose NaAsO2 exposure through the phosphorylative regulation of its downstream cell cycle regulating factors of GSK-3β/cyclin D1, p21 and p27, which could induce the promotion of cell cycle progression from G1 to S/G2M phase.
abstract_unstemmed	Arsenic is a toxic environmental contaminant. Long-term exposure to arsenic through drinking water induces human cancers. However, it is as yet uncertain about the mechanisms of arsenic induced carcinogenesis. Although the effects of low-dose arsenicals on proliferation and cell cycle have been revealed by short time exposure, the evidences for long-term exposure were seldom reported. The detailed mechanism has been unclear and supplemented constantly. In the present study, we used normal human keratinocytes (HaCat) to study the effects of long-term, low-dose sodium arsenite (NaAsO2) exposure on cell proliferation with emphasis on the Akt regulated cell cycle signaling pathways. Treatment of NaAsO2 resulted in increased cell proliferation and promotion of cell cycle progression from G1 to S/G2M phase, both of which could be attenuated by MK2206, a highly selective inhibitor of Akt. Along with the increased expression of phospho-Akt (p-Akt, Ser 473), increased expression of p-GSK-3β (Ser 9), p-p21 (Thr 145), p-p27 (Thr 157) and total cyclin D1, and decreased expression of p-cyclin D1 (Thr 286), p21 and p27 were also found in the NaAsO2 exposed cells. Treatment of MK2206 markedly reversed the expression of all of the above proteins. Our findings indicated that the phosphorylated activation of Akt played a role in the proliferation of HaCat cells upon long-term, low-dose NaAsO2 exposure through the phosphorylative regulation of its downstream cell cycle regulating factors of GSK-3β/cyclin D1, p21 and p27, which could induce the promotion of cell cycle progression from G1 to S/G2M phase.
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title_short	Akt Regulated Phosphorylation of GSK-3β/Cyclin D1, p21 and p27 Contributes to Cell Proliferation Through Cell Cycle Progression From G1 to S/G2M Phase in Low-Dose Arsenite Exposed HaCat Cells
url	https://doi.org/10.3389/fphar.2019.01176 https://doaj.org/article/dd0dfc8beb4840bca2b815f62302eeb1 https://www.frontiersin.org/article/10.3389/fphar.2019.01176/full https://doaj.org/toc/1663-9812
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Long-term exposure to arsenic through drinking water induces human cancers. However, it is as yet uncertain about the mechanisms of arsenic induced carcinogenesis. Although the effects of low-dose arsenicals on proliferation and cell cycle have been revealed by short time exposure, the evidences for long-term exposure were seldom reported. The detailed mechanism has been unclear and supplemented constantly. In the present study, we used normal human keratinocytes (HaCat) to study the effects of long-term, low-dose sodium arsenite (NaAsO2) exposure on cell proliferation with emphasis on the Akt regulated cell cycle signaling pathways. Treatment of NaAsO2 resulted in increased cell proliferation and promotion of cell cycle progression from G1 to S/G2M phase, both of which could be attenuated by MK2206, a highly selective inhibitor of Akt. Along with the increased expression of phospho-Akt (p-Akt, Ser 473), increased expression of p-GSK-3β (Ser 9), p-p21 (Thr 145), p-p27 (Thr 157) and total cyclin D1, and decreased expression of p-cyclin D1 (Thr 286), p21 and p27 were also found in the NaAsO2 exposed cells. Treatment of MK2206 markedly reversed the expression of all of the above proteins. Our findings indicated that the phosphorylated activation of Akt played a role in the proliferation of HaCat cells upon long-term, low-dose NaAsO2 exposure through the phosphorylative regulation of its downstream cell cycle regulating factors of GSK-3β/cyclin D1, p21 and p27, which could induce the promotion of cell cycle progression from G1 to S/G2M phase.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">arsenite</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Akt</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">p-GSK-3β</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">p-cyclin D1</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">p-p21</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">p-p27</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Therapeutics. Pharmacology</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Xudan Liu</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Huanhuan Wang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Shiyi Liu</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Nannan Hu</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Xin Li</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">Frontiers in Pharmacology</subfield><subfield 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Akt Regulated Phosphorylation of GSK-3β/Cyclin D1, p21 and p27 Contributes to Cell Proliferation Through Cell Cycle Progression From G1 to S/G2M Phase in Low-Dose Arsenite Exposed HaCat Cells

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