期刊
MOLECULAR CANCER RESEARCH
卷 10, 期 1, 页码 133-142出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1541-7786.MCR-11-0206
关键词
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资金
- NIH [2P01 CA098912]
- Department of Defense [W81XWH-08-1-0321]
- NATIONAL CANCER INSTITUTE [P01CA098912, R01CA122602] Funding Source: NIH RePORTER
We previously reported that sterol regulatory element-binding protein-1 (SREBP-1) is involved in the transcriptional regulation of androgen receptor (AR) and formation of fatty acid through altered expression of fatty acid synthase (FASN). In this article, we provide a new finding that SREBP-1 induced oxidative stress in prostate cancer cells through increased production of reactive oxygen species (ROS) and expression of NADPH oxidase 5 (Nox5). We have shown that (i) expression of SREBP-1 protein is positively associated with the clinical Gleason grades in human prostate cancer; (ii) genetic overexpression or knockdown of SREBP-1 in prostate cancer cells resulted in corresponding increased or decreased AR, FASN and Nox5 expression, fatty acid and lipid droplet accumulation, and ROS generation; and (iii) SREBP-1 induces and promotes the growth, migration, invasion, and castration-resistant progression of prostate cancer cells in vitro and in vivo. Our data show a novel molecular mechanism by which SREBP-1 promotes prostate cancer growth and progression through alterations in the concerted intracellular metabolic and signaling networks involving AR, lipogenesis, and ROS in prostate cancer cells. Mol Cancer Res; 10(1); 133-42. (C) 2011 AACR.
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