TRIM47基因扩增促进TNBC发生发展的分子机制研究

三阴乳腺癌和BRCA1突变的乳腺癌在表型、分子分型以及临床特征均高度相似，80%BRCA1突变的乳腺癌属于三阴乳腺癌，而只有15%的三阴乳腺癌中会出现BRCA1突变，这预示在三阴乳腺癌中BRCA1的调控存在其它机制。近期，我们的研究发现：1、TRIM47在三阴乳腺癌中显著扩增并特异性高表达，并与三阴乳腺癌的预后不良密切相关；2、TRIM47高表达可以促进三阴乳腺癌的增殖与侵袭转移；3、TRIM47蛋白与BRCA1的蛋白表达以及蛋白半衰期负相关，与其泛素化正相关；4、TRIM47高表达可以激活Wnt信号通路。然而，其具体的分子机制尚不明确。本研究拟综合分子、细胞生物学及动物模型实验，结合临床标本，深入探讨TRIM47诱导三阴乳腺癌发生发展的具体分子机制，为三阴乳腺癌的预防、诊断以及治疗提供新的分子标志物和靶点。

The phenotype, molecular typing and clinical features of triple-negative breast cancer (TNBC) and breast cancer (BC) associated with BRCA1 mutations are highly similar. However, over 80% of BC patients who carry BRCA1 mutations were diagnosed as TNBC，BRCA1 mutations were found in a low proportion (15%) of patients with TNBC. This indicates that there are other mechanisms for the regulation of BRCA1 in TNBC. Recently, we found that: 1. TRIM47 was significantly up-regulated in TNBC and closely related to poor prognosis in patients with TNBC; 2. overexpression of TRIM47 promote the proliferation and invasion of TNBC; 3. TRIM47 protein is negatively correlated with the protein expression of BRCA1 and its half-life, but positively correlated with the ubiquitination of BRCA1; 4. TRIM47 activates Wnt pathway in TNBC. However, the molecular mechanisms that TRIM47 induced the development of TNBC are still unknown. Therefore, this project aims to integrate molecular biology, cell biology and animal experimental models and analyze clinical specimen data, to further investigate the mechanisms that TRIM47 induced the development of TNBC, which may provide new biomarkers and targets for the diagnosis and treatment of TNBC.