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Acquisition of Androgen Independence by Human Prostate Epithelial Cells during Arsenic-Induced Malignant Transformation

By Webber, Mukta M.

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Book Id: WPLBN0000022646
Format Type: PDF eBook
File Size: 0.2 MB
Reproduction Date: 2005

Title: Acquisition of Androgen Independence by Human Prostate Epithelial Cells during Arsenic-Induced Malignant Transformation  
Author: Webber, Mukta M.
Volume:
Language: English
Subject: Government publications, United Nations., United Nations. Office for Disarmament Affairs
Collections: Government Library Collection, Disarmament Documents
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Publisher: United Nations- Office for Disarmament Affairs (Unoda)

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Webber, M. M. (n.d.). Acquisition of Androgen Independence by Human Prostate Epithelial Cells during Arsenic-Induced Malignant Transformation. Retrieved from http://www.ebooklibrary.org/


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Government Reference Publication

Excerpt
Excerpt: 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 prostatespecific 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. Key words: androgen independent, AR, arsenic, cancer progression, malignant transformation, prostate. Environ Health Perspect 113:1134?1139 (2005). doi:10.1289/ehp.7832 [5 May 2005].

 

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