PI-3K/Akt Pathway-Dependent Cyclin D1 Expression Is Responsible for Arsenite-Induced Human Keratinocyte Transformation.

PI-3K/Akt Pathway-Dependent Cyclin D1 Expression Is Responsible for Arsenite-Induced Human Keratinocyte Transformation. Research Abstract Details 

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PI-3K/Akt Pathway-Dependent Cyclin D1 Expression Is Responsible for Arsenite-Induced Human Keratinocyte Transformation. Abstract Text:

Weiming Ouyang,Wenjing Luo,Dongyun Zhang,Jinlong Jian,Qian Ma,Jingxia Li,Xianglin Shi,Jingyuan Chen,Jimin Gao,Chuanshu Huang,Weiming Ouyang,Wenjing Luo,Dongyun Zhang,Jinlong Jian,Qian Ma,Jingxia Li,Xianglin Shi,Jingyuan Chen,Jimin Gao,Chuanshu Huang,Weiming Ouyang,Wenjing Luo,Dongyun Zhang,Jinlong Jian,Qian Ma,Jingxia Li,Xianglin Shi,Jingyuan Chen,Jimin Gao,Chuanshu Huang,Weiming Ouyang,Wenjing Luo,Dongyun Zhang,Jinlong Jian,Qian Ma,Jingxia Li,Xianglin Shi,Jingyuan Chen,Jimin Gao,Chuanshu Huang,

BACKGROUND: Long-term exposure of arsenite leads to human skin cancer. However, the exact mechanisms of arsenite-induced human skin carcinogenesis remain to be defined. OBJECTIVES: In this study, we investigated the potential role of PI-3K/Akt/cyclin D1in the transformation of human keratinocytic cells upon arsenite exposure. METHODS: We used the soft agar assay to evaluate the cell transformation activity of arsenite exposure and the nude mice xenograft model to determine the tumorigenesis of arsenite-induced transformed cells. We used the dominant negative mutant and gene knockdown approaches to elucidate the signaling pathway involved in this process. RESULTS: Our results showed that repeated long-term exposure of HaCat cells to arsenite caused cell transformation, as indicated by anchorage-independent growth in soft agar. The tumorigenicity of these transformed cells was confirmed in nude mice. Treatment of cells with arsenite also induced significant activation of PI-3K and Akt, which was responsible for the anchorage-independent cell growth induced by arsenite exposure. Furthermore, our data also indicated that cyclin D1 is an important downstream molecule involved in PI-3K/Akt-mediated cell transformation upon arsenite exposure based on the facts that inhibition of cyclin D1 expression by dominant negative mutants of PI-3K, and Akt, or the knockdown of the cyclin D1 expression by its specific siRNA in the HaCat cells resulted in impairing of anchorage-independent growth of HaCat cells induced by arsenite. CONCLUSION: Our results demonstrate that PI-3K/Akt-mediated cyclin D1 expression is at least one key event implicated in the arsenite human skin carcinogenic effect.

PI-3K/Akt Pathway-Dependent Cyclin D1 Expression Is Responsible for Arsenite-Induced Human Keratinocyte Transformation. Publishing Authors By Initials

W Ouyang,W Luo,D Zhang,J Jian,Q Ma,J Li,X Shi,J Chen,J Gao,C Huang,W Ouyang,W Luo,D Zhang,J Jian,Q Ma,J Li,X Shi,J Chen,J Gao,C Huang,W Ouyang,W Luo,D Zhang,J Jian,Q Ma,J Li,X Shi,J Chen,J Gao,C Huang,W Ouyang,W Luo,D Zhang,J Jian,Q Ma,J Li,X Shi,J Chen,J Gao,C Huang,

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PI-3K/Akt Pathway-Dependent Cyclin D1 Expression Is Responsible for Arsenite-Induced Human Keratinocyte Transformation. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Environmental health perspectives

VOLUME: 116

Page Numbers: 1-6

Journal Abbreviation: Environ. Health Perspect.

ISSN: 0091-6765

DAY: 16

MONTH: Jan

YEAR: 2008

PI-3K/Akt Pathway-Dependent Cyclin D1 Expression Is Responsible for Arsenite-Induced Human Keratinocyte Transformation. Information

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LANGUAGE: eng

NlmUniqueID: 330411

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AFFILIATION: Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, New York, USA.

Country: United States

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MEDLINETA: Environ Health Perspect

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