文献类型：期刊文献

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

作者：Sun, Aijing[2,3];Tang, Jianxi[1];Hong, Yan[1];Song, Jiawu[1];Terranova, Paul F.[4];Thrasher, J. Brantley[1,5];Svojanovsky, Stan[6];Wang, Hong-gang[7];Li, Benyi[1,2,3,4,5]

机构：[1]Univ Kansas, Med Ctr, Dept Urol, Kansas City, KS 66160 USA;[2]Shaoxing Univ, Shaoxing Peoples Hosp, Dept Pathol, Shaoxing, Zhejiang, Peoples R China;[3]Shaoxing Univ, Affiliated Hosp 1, Shaoxing, Zhejiang, Peoples R China;[4]Univ Kansas, Med Ctr, Dept Mol & Integrated Physiol, Kansas City, KS 66103 USA;[5]Univ Kansas, Med Ctr, Kansas Mason Canc Res Inst, Kansas City, KS 66103 USA;[6]Univ Kansas, Med Ctr, Bioinformat Program, Kansas City, KS 66103 USA;[7]H Lee Moffitt Canc Ctr & Res Inst, Drug Discovery Program, Tampa, FL USA

年份：2008

卷号：68

期号：4

起止页码：453

外文期刊名：PROSTATE

收录：SCI-EXPANDED(收录号：WOS:000253882900011)、、Scopus(收录号：2-s2.0-40349087128)、WOS

语种：英文

外文关键词：prostate cancer; androgen receptor; bcl-xl; cell proliferation; xenograft

外文摘要：BACKGROUND. 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. METHODS. 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. RESULTS. 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. Genome-wide gene profiling analysis revealed that Bcl-xL expression was significantly higher in metastatic and castration-resistant diseases compared to normal prostate tissues or primary cancers. Bcl-xL overexpression significantly increased the expression of cyclin D2, which might be responsible for Bcl-xL-induced cell proliferation and tumor growth. CONCLUSIONS. Taken together, our data strongly suggest that androgen stimulates Bcl-xL expression via the AR and that increased Bcl-xL expression plays a versatile role in castration-resistant progression of prostate cancer.