Let-7a regulation of insulin-like growth factors in breast cancer
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Lingeng Lu Dionyssios Katsaros Yong Zhu Aaron Hoffman Scarampi Luca Canuto Emilie Marion Lina Mu Harvey Risch Herbert Yu
- چاپ و سال / کشور: 2010
Description
Expression of certain microRNA genes is regulated by DNA methylation, which in turn affects the activities of their downstream molecules. Our previous study showed that methylated let-7a-3 was associated with low IGF-II expression and favorable prognosis of ovarian cancer. The roles of let-7a-3 methylation in breast cancer and in regulation of IGF expression in the tumor are still unknown. Let-7a-3 methylation, IGF mRNAs, and peptides were analyzed in 348 breast cancer samples using quantitative methylation-specific PCR, qRT-PCR, and ELISA, respectively. The associations of let-7a-3 methylation with IGFs, disease features, and patient survivals were analyzed. In vitro experiments were performed using HeLa cells transfected with let-7a precursors to assess the effect of let- 7a on IGF expression. Let-7a-3 methylation was detected frequently in breast cancer. An inverse correlation between let-7a-3 methylation and IGF expression was observed in breast cancer, which was similar to that seen in ovarian cancer. Our in vitro experiment showed that let-7a could increase IGF expression in cancer cells which had low endogenous let-7a. Let-7a-3 methylation was also found to be associated with high grade tumors and ER- or PRnegative cancer. However, let-7a-3 methylation was not associated with disease-free survival or overall survival of breast cancer patients. The study provides further evidence in support of the notion that epigenetic regulation of let-7a- 3 may affect the actions of IGFs in cancer. Let-7a may upregulate the expression of IGFs in cancer cells, which is different from its inhibitory effects on other oncogenes.
Breast Cancer Res Treat (2011) 126:687–694 DOI 10.1007/s10549-010-1168-5 Received: 28 July 2010 / Accepted: 4 September 2010 / Published online: 17 September 2010 Springer Science+Business Media, LLC. 2010
