SUMO化修饰对AhR的调控及在乳腺癌发生、发展中的作用

项目名称： SUMO化修饰对AhR的调控及在乳腺癌发生、发展中的作用

项目编号： No.31271500

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 伍会健

作者单位： 大连理工大学

项目金额： 80万元

中文摘要： 二噁英TCDD是一种毒性较强的类雌激素物质，能诱导乳腺癌的发生。二噁英是通过与属于核受体家族成员的芳香烃受体AhR结合，进而调控AhR下游靶基因的表达来实现其功能的。对二噁英的毒性研究尽管进行了多年，但对其分子机理仍知之不多，是世界范围的研究热点和难点，因此研究AhR的活性是如何被调控的，是弄清TCDD诱导乳腺癌发生、发展分子机理非常重要的一环。我们的研究初步证明AhR是SUMO化修饰的靶蛋白，SUMO化修饰对AhR的转录活性起抑制作用，因此，进一步的研究，不仅可以揭示核受体的基因调控网络，还将有助于我们更好地了解转录相关因子的SUMO化修饰在乳腺癌发生、发展的分子机理，为乳腺癌的治疗提供新的思路和靶标。

中文关键词： 芳香烃受体；SUMO；雌激素受体；乳腺癌；

英文摘要： 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an estrogen-like hormone, but has greater toxicity that can induce the development of breast cancer. TCDD binds to the aromatic hydrocarbon receptor AhR (which belongs to the nuclear receptor superfamily) and regulates the subsequent expression of its downstream genes. Although the toxicity of TCDD has been investigated for many years, little is known about its molecular mechanism, which is difficult to study and has been considered as a hot research topic world-wide. Thus research focusing on how the activity of AhR can be regulated is a key link to understand the molecular mechanism of TCDD-induced breast cancer. Our preliminarily research has shown that AhR can be sumoylated, and sumoylation of AhR has a negative effect on its transcriptional activity. So further study will not only reveal the gene regulation network of nuclear receptor, but will also allow us to better understand the molecular mechanisms of transcriptional factors that are modified by SUMO in the generation and development of breast cancer. It may also provide new insight and target for potential breast cancer therapy.

英文关键词： aryl hydrocarbon receptor；SUMO；estrogen receptor；breast cancer；