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• W2061620439 startingPage "1134" @default.
• W2061620439 abstract "Lethal phenotypes of human prostate cancer are characterized by progression to androgen independence, although the mechanisms behind this progression remain unclear. Arsenic is a potential human prostate carcinogen that may affect tumor progression. In this study, we used a prostate cancer cell model in which an immortalized, nontumorigenic human prostate epithelial cell line (RWPE-1) had been malignantly transformed by chronic low-level arsenic to help determine whether arsenic affects prostate tumor progression. Control and CAsE-PE (chronic-arsenic–exposed human prostate epithelial) cells were continuously maintained in a complete medium [keratinocyte serum-free medium (K-SFM) with bovine pituitary extract and epidermal growth factor] or in a steroid-depleted medium (K-SFM alone). The arsenic-transformed cells showed a more rapid proliferation rate in complete medium than did control cells and also showed sustained proliferation in steroid-reduced medium. Although both control and CAsE-PE cells showed similar levels of androgen receptor (AR), androgens were less effective in stimulating cell proliferation and AR-related gene expression in CAsE-PE cells. For instance, dihydrotestosterone caused a 4.5-fold increase in prostate-specific antigen transcript in control cells but only a 1.5-fold increase in CAsE-PE cells. CAsE-PE cells also showed relatively low levels of growth stimulation by nonandrogen steroids, such as estradiol. Thus, arsenic-induced malignant transformation is associated with acquired androgen independence in human prostate cells. This acquired androgen independence was apparently not due to AR up-regulation, increased activity, or altered ligand specificity. The precise manner in which arsenic altered CAsE-PE growth and progression is undefined but may involve a bypass of AR involving direct stimulation of downstream signaling pathways." @default.
• W2061620439 created "2016-06-24" @default.
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• W2061620439 date "2005-09-01" @default.
• W2061620439 modified "2023-09-26" @default.
• W2061620439 title "Acquisition of Androgen Independence by Human Prostate Epithelial Cells during Arsenic-Induced Malignant Transformation" @default.
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• W2061620439 doi "https://doi.org/10.1289/ehp.7832" @default.
• W2061620439 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1280391" @default.
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