Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin Medical University Cancer Hospital, Tianjin, China.
Biochem Biophys Res Commun. 2010 Mar 26;394(1):59-63. doi: 10.1016/j.bbrc.2010.02.093. Epub 2010 Feb 18.
The aim was to analyze the mechanism of leptin-induced activity of telomerase in MCF-7 breast cancer cells. We found that leptin activated telomerase in a dose-dependent manner; leptin upregulated the expression of Human Telomerase Reverse Transcriptase (hTERT) at mRNA and protein levels; blockade of signal transducer and activator of transcription 3 (STAT3) phosphorylation significantly counteracted leptin-induced hTERT transcription and protein expression; chromatin immunoprecipitation analysis showed that leptin enhanced the binding of STAT3 to the hTERT promoter. This study uncovers a new mechanism of the proliferative effect of leptin on breast cancer cells and provides a new explanation of obesity-related breast cancer.
目的在于分析瘦素诱导 MCF-7 乳腺癌细胞端粒酶活性的机制。我们发现瘦素呈剂量依赖性地激活端粒酶;瘦素上调 hTERT 在 mRNA 和蛋白水平的表达;信号转导和转录激活因子 3(STAT3)磷酸化阻断明显拮抗瘦素诱导的 hTERT 转录和蛋白表达;染色质免疫沉淀分析表明,瘦素增强了 STAT3 与 hTERT 启动子的结合。本研究揭示了瘦素对乳腺癌细胞增殖作用的新机制,并为肥胖相关乳腺癌提供了新的解释。