ROS介导的RECK表遗传沉默在27羟基胆固醇促进乳腺癌侵袭转移中的作用

高脂高胆固醇饮食引起的高胆固醇血症是绝经后妇女患乳腺癌的独立危险因素。最近研究表明，胆固醇代谢物27羟基胆固醇（27HC）是联系高胆固醇血症与乳腺癌的关键分子。27HC是一种代谢产生的内源性雌激素，和雌二醇一样，可发挥雌激素效应促进雌激素受体阳性乳腺癌生长。但我们发现，不同于雌二醇，27HC可促进乳腺癌侵袭转移，其原因尚不清楚。本研究拟采用雌激素剥夺乳腺癌细胞模型和去卵巢裸鼠乳腺癌动物模型（模拟绝经后），探讨活性氧（ROS）对RECK的表遗传沉默作用，RECK对IL-6/STAT3信号调控机制，STAT3激活与侵袭转移的关系。以验证“27HC通过ROS沉默RECK促进乳腺癌侵袭转移”的新观点。弄清27HC促进侵袭转移的原因，采取针对性预防和干预措施，阻断27HC引起的健康危害，对肥胖和绝经后代谢综合征乳腺癌人群至关重要。同时，对预防肥胖和绝经后代谢综合征妇女的乳腺癌发生风险具有重要意义。

High fat, high cholesterol diet-induced hypercholesterolemia is an independent risk factor for estrogen receptor (ER)–positive breast cancers in postmenopausal women. 27-Hydroxycholesterol（27HC）, an abundant primary metabolite of cholesterol, recently is associated with the occur and development of breast cancer. Same as 17b-estradiol, 27HC was sufficient to promote the growth of breast cancer via the estrogenic activity. In our recent preliminary investigations, we have demonstrated that, unlike 17b-estradiol, 27HC could induce the migration, invasion and angiogenesis of breast cancer cells in vitro. but the mechanisms are still unclear. This project plans to investigate the effects of 27HC on ROS (Reactive oxygen species)-induced epigenetic seliencing of RECK gene, the potential mechanisms involved in the regulation of IL-6/STAT3 signal by RECK, the association between p-STAT3 and migration/invasion in estrogen-deprived cell model and ovariectomized athymic mice model. To confirm the effects that 27HC on the migration, invasion and angiogenesis of breast cancer cells. This research will give us further informations about the health effects of 27HC on the patients with estrogen-dependent breast cancer.