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首页> 美国政府科技报告 >Fatty Acid Synthesis and Prostate Cancer: Hormonal Regulation and Anti- Metabolite targeting of an Acquired Function in Neoplasia.
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Fatty Acid Synthesis and Prostate Cancer: Hormonal Regulation and Anti- Metabolite targeting of an Acquired Function in Neoplasia.

机译：脂肪酸合成和前列腺癌：激素调节和抗代谢物靶向肿瘤中获得性功能。

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The overall goal of this project is to determine the regulatory mechanisms that activate fatty acid (FA) synthetic metabolism during malignant progression of prostate cancer, and to evaluate FA synthesis as a therapeutic target. The biosynthetic enzyme, fatty acid synthase (FAS), is expressed at elevated levels in PCa cells and is a marker of tumors with activated FA synthesis. While PAS expression is androgen responsive, it persists or is reactivated in tumors after androgen ablation, and is high in 83% of lethal tumors examined at autopsy. Experimental model systems of PCa (in vitro and in vivo) show similar patterns of PAS activation, with increased PAS during progression to androgen independence. Tumor cell changes in fatty acid metabolism are insensitive to nutritional regulation, and tumor cells produce predominantly membrane lipids. Our experiments have led to the observation that growth factor signals mediated by activated kinases in PCa cells and transformation models activate the fatty acid synthesis pathway via modulation of SREBP-lc transcription factor levels, resulting in the tumor phenotype of activated PA metabolism that is insensitive to nutritional regulation. Small molecules that inhibit PAS are cytotoxic to tumors, and the mechanism of tumor cell killing is under investigation.

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