乙酰基转移酶ARD1与乳腺癌扩大因子AIB1的相互作用及其在乳腺癌中的角色

项目名称： 乙酰基转移酶ARD1与乳腺癌扩大因子AIB1的相互作用及其在乳腺癌中的角色

项目编号： No.81460402

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 晏姗

作者单位： 昆明医科大学

项目金额： 50万元

中文摘要： ARD1是一个乙酰基转移酶，参与了细胞内多种生命过程，它在肿瘤中的角色一直备受关注，却也充满争议。我们发现ARD1在乳腺癌组织和多种乳腺癌细胞中表达升高。用短的发夹RNA沉默ARD1能够抑制乳腺癌细胞增殖和裸鼠移植瘤生长。酵母双杂交实验证实乳腺癌扩大因子AIB1与ARD1有相互作用。AIB1与乳腺癌的恶化进程密切相关，其促癌作用主要是依赖转录共激活作用来实现。实验提示AIB1很可能是ARD1的底物，ARD1乙酰化修饰AIB1，提高其转录共激活功能，开启细胞增殖信号通路，从而促进了乳腺癌的发展。本课题拟利用乳腺癌临床标本、细胞模型和动物模型，研究ARD1与AIB1相互作用的性质及其对乳腺癌发展的影响，以期揭示ARD1通过对特定底物蛋白的乙酰化修饰和相应的信号转导途径在细胞中发挥促癌作用的机制，为理解ARD1在肿瘤中的不同角色提供依据，也为认识乳腺癌的发病原因和寻找可能的干预靶点提供新的线索。

中文关键词： C21_乳腺肿瘤；ARD1；乙酰化；AIB1

英文摘要： Arrest-defective protein1 (ARD1), as an acetyltransferase, is involved in a variety of cellular functions。It has been reported to play a crucial role in tumorigenesis, but the results are somewhat controversial. We found that ARD1 is up-regulated in human mammary carcinoma cell lines and primary tumor biopsies. Depletion of ARD1 by shRNA suppressed mammary carcinoma cell proliferation and xenograft tumor formation in nude mice. Amplified in breast cancer 1 (AIB1) was identified to bind ARD1 in yeast two-hybrid system. AIB1 is a transcriptional coactivator that mediates the transcriptional activities of nuclear receptors and other transcription factors. It plays a key role in the development and progression of several different cancers. Preliminary data indicate the AIB1 acetylation and enhancement activity by ARD1. In this research we will elucidate the role of ARD1 in the AIB1 signaling transduction and in the development of breast cancer, which is helpful not only in providing a new strategy for breast cancer treatment, but also facilitating further understanding status of ARD1 in cancer development.

英文关键词： breast cancer;ARD1;Acetylation;AIB1