Androgen receptor-dependent regulation of Bcl-xL expression: Implication in prostate cancer progression

The Prostate
Aijing SunBenyi Li

Abstract

Recently we reported that silencing the androgen receptor (AR) gene reduced Bcl-xL expression that was associated with a profound apoptotic cell death in prostate cancer cells. In this study we further investigated AR-regulated Bcl-xL expression. Prostate cancer cell line LNCaP and its sublines, LNCaP/PURO and LNCaP/Bclxl, were used for cell proliferation assay and xenograft experiments in nude mice. Luciferase gene reporters driven by mouse or human bcl-x gene promoter were used to determine androgen regulation of Bcl-xL expression. RT-PCR and Western blot assays were conducted to assess Bcl-xL gene expression. Chromatin immunoprecipitation assay was performed to determine AR interaction with Bcl-xL promoter. Bcl-xL-induced alteration of gene expression was examined using cDNA microarray assay. In cultured prostate cancer LNCaP cells, androgen treatment significantly increased Bcl-xL expression at mRNA and protein levels via an AR-dependent mechanism. Promoter analyses demonstrated that the AR mediated androgen-stimulated bcl-x promoter activation and that the AR interacted with bcl-x promoter. Enforced expression of Bcl-xL gene dramatically increased cell proliferation in vitro and promoted xenograft tumor growth in vivo. Gen...Continue Reading

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Citations

Nov 1, 2013·Journal of the National Cancer Institute·Cheng LiuYidong Fan
Jan 23, 2013·The Cancer Journal·Robert R ZielinskiKim N Chi
Jul 16, 2009·Journal of Experimental & Clinical Cancer Research : CR·Huaifu LiMing Zhan
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Mar 7, 2021·Cancers·Amaal Ali, George Kulik
Apr 25, 2009·Current Opinion in Endocrinology, Diabetes, and Obesity

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