缺氧诱导因子-1α对前列腺癌脂代谢的调控

Lipid metabolism regulated by hypoxia inducible factor -1α in prostate cancer

目的探讨缺氧诱导因子-1α（HIF-1α）对前列腺癌细胞脂代谢的作用及其调控机制。方法通过实时定量聚合酶链反应（FQ-PCR）与Westernblot法比较不同前列腺癌细胞中HIF-1α与脂肪合成基因的表达。在此基础上通过缺氧环境（1％O2）培养与转染HIF-1α突变质粒，分析脂肪合成基因的表达。并且通过荧光素酶报告基因与染色质免疫沉淀方法探讨该变化的分子机制。结果在前列腺癌细胞中，HIF-1α与脂肪合成基因的表达明显相关。前列腺癌细胞在缺氧条件下以及转染HIF-1α突变质粒的条件下均可促进脂肪合成基因的表达。HIF-1α可以结合到胆固醇调节元件结合蛋白（SREBP）-1c的启动子区域促进其转录。与对照组比较（1．000±0．095、1．000±0．042），HIF-1α可以显著升高SREBP-1c的mRNA（2．992±0．159）与蛋白质（2．349±0．114）的表达水平。结论缺氧环境中，HIF-1仪会通过激活SREBP-1c转录，从而促进前列腺癌细胞的从头脂肪合成。

Objective To investigate the effects and mechanisms of hypoxia inducible factor - 1α （ HIF - 1α） on lipid metabolism in prostate cancer cells. Methods The expression of HIF - 1α and lipo- genic genes were compared in different prostate cancer cell lines by real - time fluorescent quantitative poly- merase chain reaction （ FQ - PCR） and Western blotting. Then the expression of lipogenic genes in prostate cancer cells under hypoxic environment or transfected with HIF - let - Mutant plasmid was analyzed. In addi- tion, luciferase assay and ChIP assay were used to determined the underlying molecular mechanisms. Results There is some correlation between HIF - 1α and lipogenic genes. Hypoxic environment and overexpression of HIF - let could increase the level of lipogenic genes. HIF -1α could bind to the promoter of sterol - regula- tory element binding proteins （SREBP） - lc and regulate its transcription. Compared to negative control （ 1.000±0. 095, 1.000 ±0. 042）, HIF - let could significant increase the mRNA （2. 992 ±0. 159） and pro- tein （2. 349 ± 0. 114） levels of SREBP - 1 c. Conclusion In hypoxic environment, HIF - 1α could promote de novo ligogenesis through promote the transcription of SREBP -1 c in prostate caener cells.