Smurf1蛋白调节乳腺癌雌激素信号通路的机制研究

乳腺癌是女性发病率第一位的恶性肿瘤，其中雌激素受体阳性者占60%-70%。雌激素受体阳性乳腺癌治疗的经典药物是他莫昔芬，但是他莫昔芬的长期使用会诱导乳腺癌的耐药。之前的大量研究已经证明雌激素受体本身的翻译后修饰与他莫昔芬耐药有显著的相关性。Smurf1在肿瘤细胞的细胞周期、增殖、分化、代谢、基因组稳定性、老化等方面具有作用。但Smurf1对于ERα通路的作用机制尚不明确。我们的初步研究结果显示Smurf1参与调节ERα信号通路。本课题通过使用实时定量PCR、免疫印迹、免疫共沉淀和泛素化相关免疫共沉淀方法，旨在研究Smurf1对ERα蛋白的翻译后调节以及ERα通路活性调节的分子机制，为乳腺癌的治疗以及逆转内分泌治疗耐药提供新的思路。

Breast cancer is the most common cancer in women. Among them, 60%-70% percent are ER (estrogen receptor) positive. Tamoxifen is a classical treatment for ER positive breast cancer. However, tamoxifen resistance will develop during the long time treatment. The post-translational modification of ERα protein has been linked with tamoxifen resistance. Smurf1 has different functions in cell cycle, proliferation, differentiation, metabolism, genomic stability, aging and so on. However, the Smurf1 function in ERα pathway is still unclear. Our primary data shows that Smurf1 modulates ERα signaling. In this project, we use different methods (such as RT-qPCR, western blot, immunoprecipitation, and ubiquitination related mmunoprecipitation) to investigate the mechanism of Smurf1 in ERα pathway, which will contribute to the understanding of breast cancer and tamoxifen resistance.