PI-3K/Akt pathway-dependent cyclin D1 expression is responsible for arsenite-induced human keratinocyte transformation

Environmental Health Perspectives
Weiming OuyangChuanshu Huang

Abstract

Long-term exposure of arsenite leads to human skin cancer. However, the exact mechanisms of arsenite-induced human skin carcinogenesis remain to be defined. In this study, we investigated the potential role of PI-3K/Akt/cyclin D1in the transformation of human keratinocytic cells upon arsenite exposure. 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. 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...Continue Reading

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Citations

Mar 8, 2011·Omics : a Journal of Integrative Biology·Shilpa TyagiYogeshwer Shukla
Dec 23, 2017·Journal of Medicinal Food·Van-Long TruongWoo-Sik Jeong
May 7, 2020·Metallomics : Integrated Biometal Science·Xinyang LiZunzhen Zhang
Jul 31, 2012·The Journal of Biological Chemistry·Hong-Gyum KimZigang Dong
Jan 23, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Raihan KabirMark J Kohr

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Methods Mentioned

BETA
transfect
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