PRMT2在三阴乳腺癌中对ERα36受体介导的细胞自噬调控机制研究

The triple negative breast carcinoma is a special subtype of breast cancer, which has the characteristics of high ability of invasion and easy to migrate or relapse. However, there still is absence of effective means of molecular targeted therapy. ERα36 is a new isoform of ERα in resent discovery. It is closely related to the progress, prognosis and drug resistance generated in breast cancer. Previous research shows that PRMT2 can inhibit the proliferation of breast cancer cells. But the exact mechanism remains unclear. Our data showed that PRMT2 had low expression in triple negative breast carcinoma and autophagy could be induced by overexpression of PRMT2 in triple negative breast carcinoma cells. For this, we propose the following scientific hypothesis that PRMT2 can promote the autophagic activity and inhibit the proliferation of breast cancer cell through ERα36. In the current study, triple negative breast carcinoma cells are chose to research. Slow virus infection and gene transfection technique are applied to observe influence of high expression of PRMT2 on autophagy, proliferation and tumor formation in nude mice. Double report gene detection and chromatin immunoprecipitation technology are carried out to analyze influence of PRMT2 on the key factors of autophagy pathway. Finally, we plan to explore expression of PRMT2 and its clinical significance in triple negative breast carcinoma tissue. In a word,the successful completion of the project is expected to clarify the molecular mechanism of PRMT2 mediating autophagy through receptor of ERα36 and provide new strategies for targeted therapy of triple negative breast carcinoma.

三阴乳腺癌具有侵袭性高、易转移复发等特点，目前仍缺乏有效的分子靶向治疗手段。ERα36是最近发现的一种ERα亚型，参与乳腺癌的进展、预后及耐药生成。研究发现，PRMT2能抑制乳腺癌细胞增殖，但具体机制未明。申请者前期研究证实PRMT2在三阴乳腺癌中呈低表达，过表达PRMT2能诱导三阴乳腺癌细胞的自噬活性。为此，我们提出如下科学假说："PRMT2诱导ERα36介导的自噬活性，抑制乳腺癌细胞增殖。"本课题拟选用三阴乳腺癌细胞为研究对象，采用慢病毒感染与基因转染技术，观察PRMT2高表达对三阴性乳腺癌细胞自噬、增殖及裸鼠成瘤的影响；采用双报告基因检测与染色质免疫沉淀技术分析PRMT2对自噬途径关键因子的影响；探讨PRMT2在三阴性乳腺癌组织中的表达及临床意义。本项目的完成有望阐明PRMT2通过ERα36受体介导调控三阴乳腺癌细胞自噬的分子机制，为三阴乳腺癌靶向治疗提供新策略。

三阴乳腺癌具有侵袭性高、易转移复发等特点，目前仍缺乏有效的分子靶向治疗手段。ERα36是最近发现的一种ERα亚型，参与乳腺癌的进展、预后及耐药生成。研究发现，PRMT2能抑制乳腺癌细胞增殖，但具体机制未明。申请者前期研究证实PRMT2在三阴乳腺癌中呈低表达，过表达PRMT2能诱导三阴乳腺癌细胞的自噬活性。为此，我们提出如下科学假说：“PRMT2诱导ERα36介导的自噬活性，抑制乳腺癌细胞增殖。”本课题拟选用三阴乳腺癌细胞为研究对象，采用慢病毒感染与基因转染技术，观察PRMT2高表达对三阴性乳腺癌细胞自噬、增殖及裸鼠成瘤的影响；采用双报告基因检测与染色质免疫沉淀技术分析PRMT2对自噬途径关键因子的影响；探讨PRMT2在三阴性乳腺癌组织中的表达及临床意义。本项目的完成有望阐明PRMT2通过ERα36受体介导调控三阴乳腺癌细胞自噬的分子机制，为三阴乳腺癌靶向治疗提供新策略。