潜在原癌基因MERIT40/NBA1在乳腺癌发生、发展中的功能和机制研究

Breast cancer is a type of malignant cancer originating from the abnormal proliferation of breast tissue. We have identified a new protein, MERIT40/NBA1, in BRCA1 associated A complex and propose it as an oncogene candidate for mammary cells tumorigenesis. In this study, we will first determine the expression profile of MERIT40/NBA1 gene in mammary normal and tumor tissues. We also propose to analyze the biological properties of MERIT40/NBA1 in mammary cells, including the proliferation, differentiation and cellular polarity. If MERIT40/NBA1 is a potential oncogene, we will examine its conserved domains to further understand its biochemical function. Finally, we will investigate the MERIT40/NBA1's molecular mechanism and downstream pathways in the breast tumorigenesis and validate this gene as a new target for breast cancer therapeutics. All of the experiments proposed in this project have relevance to breast tumorigenesis through careful examination of the biology role of MERIT40/NBA1 in mammary cells with the goal of finding new drug targets that will promote survival of breast cancer patients.

乳腺癌是一种严重威胁女性健康的恶性肿瘤, 通常源于乳腺细胞的恶性转化、无序生长。我们已有的研究提示乳腺癌易感基因1（BRCA1）相关A蛋白复合物中的MERIT40/NBA1亚基携带有原癌基因的部分生物学特性，参与了乳腺癌发生和转化过程。本课题拟针对MERIT40/NBA1基因的生物学特性，运用遗传学和分子生物学技术开展研究, 揭示MERIT40/NBA1在乳腺癌发生和发展中的重要生物学功能。课题将包括：MERIT40/NBA1基因肿瘤表达谱的研究；MERIT40/NBA1基因对于乳腺细胞生长，分化以及细胞极性的影响；MERIT40/NBA1基因关键功能域的分析；MERIT40/NBA1基因下游信号通路及其分子机制；以及作为新型乳腺癌靶点的可行性研究。本研究的成果将最终揭示MERIT40/NBA1基因与乳腺癌发生和发展的内在联系，探讨该基因作为新型乳腺癌治疗靶点的可能性。

乳腺癌是一种严重威胁女性健康的恶性肿瘤, 通常源于乳腺细胞的恶性转化、无序生长。本课题研究发现乳腺癌易感基因1（BRCA1）相关A 蛋白复合物中的MERIT40/NBA1 亚基携带有原癌基因的部分生物学特性，参与了乳腺癌发生和转化过程。本研究的内容为：1) MERIT40/NBA1 基因乳腺肿瘤表达谱特征；2）MERIT40/NBA1 基因对于乳腺细胞生长，分化的影响；3）MERIT40/NBA1 基因关键功能域的分析；4）MERIT40/NBA1 基因下游信号通路及其分子机制；5）NBA1基因及其相关BRCA1-A复合体所含基因的多态性与三阴性乳腺癌发生进行了关联研究。本研究的研究成果部分揭示了MERIT40/NBA1 基因与乳腺癌发生和发展的联系及内在分子机制。