报告题目：The p160 Steroid Receptor Coactivator (SRC) Family and Breast Cancer
报告人： Jian-ming Xu，美国贝勒医学院分子与细胞生物学系教授
主持人： 李晓涛 教授
报告时间：9月4日 14:00（周二）
报告地点：闵行生命科学学院大楼534报告厅
报告人简介：Jian-ming Xu博士，美国贝勒医学院分子与细胞生物学系教授。Jian-ming Xu于1994年获得美国Clarkson大学生物化学和细胞分子生物学博士学位，1994至1997年在贝勒医学院细胞生物学系担任博士后工作，期间获得美国国立卫生中心授予的个人研究服务博士后奖学金。现为美国贝勒医学院分子与细胞生物学系教授。
报告内容简介：The p160 SRC family contains three potent transcriptional coactivators for nuclear hormone receptors such as estrogen, progesterone and androgen receptors and certain other transcription factors such as E2F1, PEA3, AP-1 and HIF1. These p160 coactivators are expressed at low levels in normal mammary epithelial cells. However, the expression of SRC-1 and SRC-3 are significantly elevated in subsets of human breast cancers and their overexpressions are usually associated with disease recurrence, metastasis, endocrine therapy resistance and reduced disease-free survival. Using various genetically engineered breast cancer mouse models induced by oncogene expression or chemical carcinogen treatment and breast cancer cell line models, we found that knockout of SRC-1 specifically suppresses polyoma middle T (PyMT)-induced mammary tumor cell metastasis without affecting primary mammary tumor initiation and growth; knockout of SRC-2 has no effect on PyMT-induced mammary tumor development and metastasis; and knockout of SRC-3 represses mammary tumor initiation, growth and metastasis induced by oncogenes including PyMT and Ras and a chemical carcinogen. These results suggest that each SRC coactivator has a distinct role in breast cancer. Our laboratory also investigated the molecular mechanisms responsible for SRC-1 and SRC-3 to promote breast cancer growth and/or metastasis. We found that SRC-1 and SRC-3 serve as potent coactivators for multiple transcription factors including PEA3, AP-1 and HIF1 to directly upregulate Twist, integrin 5alpha, MMP2, MMP9, CSF-1 and/or VEGF, which in turn drives breast cancer cell epithelial mesenchymal transition (EMT), migration, invasion and metastasis.