期刊
CANCER CELL
卷 20, 期 4, 页码 457-471出版社
CELL PRESS
DOI: 10.1016/j.ccr.2011.09.001
关键词
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资金
- National Institutes of Health [R01 CA111803, P50 CA090381, R00 CA135592, P50 CA097186, RO1 CA146849]
- Department of Defense [PC060807, PC093509]
- Prostate Cancer Foundation
Androgen receptor (AR) is reactivated in castration-resistant prostate cancer (CRPC) through mechanisms including marked increases in AR gene expression. We identify an enhancer in the AR second intron contributing to increased AR expression at low androgen levels in CRPC. Moreover, at increased androgen levels, the AR binds this site and represses AR gene expression through recruitment of lysine-specific demethylase 1 (LSD1) and H3K4me1,2 demethylation. AR similarly represses expression of multiple genes mediating androgen synthesis, DNA synthesis, and proliferation while stimulating genes mediating lipid and protein biosynthesis. Androgen levels in CRPC appear adequate to stimulate AR activity on enhancer elements, but not suppressor elements, resulting in increased expression of AR and AR repressed genes that contribute to cellular proliferation.
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