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

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 mode...

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Detalles Bibliográficos
Autores principales: Benbrahim-Tallaa, Lamia, Webber, Mukta M., Waalkes, Michael P.
Formato: Texto
Lenguaje:English
Publicado: National Institute of Environmental Health Sciences 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1280391/
https://www.ncbi.nlm.nih.gov/pubmed/16140617
http://dx.doi.org/10.1289/ehp.7832
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author Benbrahim-Tallaa, Lamia
Webber, Mukta M.
Waalkes, Michael P.
author_facet Benbrahim-Tallaa, Lamia
Webber, Mukta M.
Waalkes, Michael P.
author_sort Benbrahim-Tallaa, Lamia
collection PubMed
description 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.
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spelling pubmed-12803912005-11-30 Acquisition of Androgen Independence by Human Prostate Epithelial Cells during Arsenic-Induced Malignant Transformation Benbrahim-Tallaa, Lamia Webber, Mukta M. Waalkes, Michael P. Environ Health Perspect Research 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. National Institute of Environmental Health Sciences 2005-09 2005-05-05 /pmc/articles/PMC1280391/ /pubmed/16140617 http://dx.doi.org/10.1289/ehp.7832 Text en http://creativecommons.org/publicdomain/mark/1.0/ Publication of EHP lies in the public domain and is therefore without copyright. All text from EHP may be reprinted freely. Use of materials published in EHP should be acknowledged (for example, ?Reproduced with permission from Environmental Health Perspectives?); pertinent reference information should be provided for the article from which the material was reproduced. Articles from EHP, especially the News section, may contain photographs or illustrations copyrighted by other commercial organizations or individuals that may not be used without obtaining prior approval from the holder of the copyright.
spellingShingle Research
Benbrahim-Tallaa, Lamia
Webber, Mukta M.
Waalkes, Michael P.
Acquisition of Androgen Independence by Human Prostate Epithelial Cells during Arsenic-Induced Malignant Transformation
title Acquisition of Androgen Independence by Human Prostate Epithelial Cells during Arsenic-Induced Malignant Transformation
title_full Acquisition of Androgen Independence by Human Prostate Epithelial Cells during Arsenic-Induced Malignant Transformation
title_fullStr Acquisition of Androgen Independence by Human Prostate Epithelial Cells during Arsenic-Induced Malignant Transformation
title_full_unstemmed Acquisition of Androgen Independence by Human Prostate Epithelial Cells during Arsenic-Induced Malignant Transformation
title_short Acquisition of Androgen Independence by Human Prostate Epithelial Cells during Arsenic-Induced Malignant Transformation
title_sort acquisition of androgen independence by human prostate epithelial cells during arsenic-induced malignant transformation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1280391/
https://www.ncbi.nlm.nih.gov/pubmed/16140617
http://dx.doi.org/10.1289/ehp.7832
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