LEF1 in androgen-independent prostate cancer: regulation of androgen receptor expression, prostate cancer growth, and invasion.
LEF1 in androgen-independent prostate cancer: regulation of androgen receptor expression, prostate cancer growth, and invasion.
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DOI：
10.1158/0008-5472.can-08-3380
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发表时间：
2009-04-15
期刊：
影响因子：
11.2
通讯作者：
Lee P
中科院分区：
文献类型：
--
作者：
Li Y;Wang L;Zhang M;Melamed J;Liu X;Reiter R;Wei J;Peng Y;Zou X;Pellicer A;Garabedian MJ;Ferrari A;Lee P
A major obstacle in treating prostate cancer is the development of androgen-independent disease. In this study, we examined LEF1 expression in androgen-independent cancer as well as its regulation of androgen receptor (AR) expression, prostate cancer growth and invasion in androgen-independent prostate cancer cells. Affymetrix microarray analysis of LNCaP and LNCaP-AI (androgen-independent variant LNCaP) cells revealed 100-fold increases in LEF1 expression in LNCaP-AI cells. We showed that LEF1 overexpression in LNCaP cells resulted in increased AR expression and consequently enhanced growth and invasion ability, while LEF1 knockdown in LNCaP-AI cells decreased AR expression and subsequently the growth and invasion capacity. Chromatin immunoprecipitation, gel shift, and luciferase assays confirmed LEF1 occupancy and regulation of the AR promoter. Thus, we identified LEF1 as a potential marker for androgen independent disease and a key regulator of AR expression and prostate cancer growth and invasion. LEF1 is highly expressed in androgen-independent prostate cancer, potentially serving as a marker for androgen-independent disease.
