ERα的磷酸化修饰能够精确的调控其转录活性，在乳腺癌的发生发展及内分泌治疗耐药等方面扮演重要角色。因此，分离鉴定靶向ERα的蛋白激酶对于阐明乳腺癌耐药的分子机制至关重要。我们前期研究发现参与有丝分裂纺锤体组装检查点的重要激酶Mps1能与ERα发生相互作用,过表达Mps1通过诱导ERα发生丝氨酸磷酸化上调ERα的转录活性。进一步研究表明，Mps1高表达细胞呈现生长优势，而且对他莫昔芬诱导的细胞死亡不敏感。这些研究提示我们，Mps1很有可能通过磷酸化修饰ERa这种新的调控方式参与乳腺癌的发展及内分泌耐药。本项目拟进一步研究Mps1通过ERα的磷酸化调控其转录活性的分子机制，评估二者相互作用对乳腺癌细胞转移、侵袭以及成瘤的影响，并通过临床标本及已经发表的数据库，分析Mps1磷酸化ERα与临床病理分期、乳腺癌耐药及预后的关系，揭示Mps1在乳腺癌发生中的重要意义及可能的分子机制。

Estrogen receptors are members of the steroid hormone superfamily of nuclear receptors that act as ligand-activated transcription factors. Like other steroid hormone receptors, estrogen receptor α is a substrate for protein kinases, and phosphorylation has profound effects on the function of this receptor and endocrine resistance. However, the contributions of specific kinases in endocrine resistance are still not fully understood. Our previous work showed that ERα associates with Mps1, an important kinase in spindle assembly checkpoint. Erα phosphorylation by Mps1 led to enhanced ERα transcriptional activity and increased resistance to tamoxifen treatment. Taken together, we would like to explore further the interaction of Mps1 with ERα and their biological significance, elucidating the molecular mechanism of Mps1 in endocrine resistance in breast cancer. Furthermore, the importance of Mps1 in endocrine resistance and the usefulness as a therapeutic target for breast cancer could be uncovered through the correlation study between Mps1 and ERα protein expression from a large cohort of subjects with breast cancer.