PES1与雌激素受体存在相互作用

雌激素(E2)和雌激素受体(ER)在E2诱发的肿瘤中起着极其重要的作用.ER共调节因子通过与ER相互作用调节其生物学功能.PES1主要表达于E2的重要靶器官如乳腺、卵巢等组织中,并在乳腺癌细胞中高表达.用PCR技术构建HA标签的PES1全长以及1～322aa、312 ～588aa和414～588aa三个不同功能区片段的重组质粒.将不同的重组质粒与FLAG-ERα和或FLAGC-ERβ共转染293T细胞后进行免疫共沉淀,以验证PES1与ER是否有相互作用以及相互作用的区域.用含雌激素受体作用元件的荧光素酶报告基因( ERE-LUC)检测PES1对ERα和ERβ转录激活活性的影响.结果表明,PES1与ERα和ERβ均相互作用,且PES1的1～ 322aa区域与ERα和ERβ相结合.PES1能特异地、E2非依赖性抑制ERβ的转录激活活性.实验结果显示,PES1是一个新的ER共调节因子,需要进一步研究其在ERβ信号通路及其在E2诱发的肿瘤的作用.

PES1 Interacts with Estrogen Receptor

Estrogen(E2) and estrogen receptors(ER) play a vital role in the E2-induced neoplasms.The coregulators of ERs modulate their biological functions by binding these receptor.PES1,as a potential regulator,is mainly expressed in the target organs such as breast and ovarian,and also,is highly expressed in the breast cancer cells.In current work,the HA-tagged recombinant plasmids of full-length PES1,and its different function regions(1~322aa,312~588aa and 414~588aa) were constructed by PCR.To test whether PES1 can interact with ERs and their interaction regions,different recombinant plasmids constructed were co-transfected with FLAG-ERα or/and FLAGC-ERβ in 293T cells before co-immunoPrecipitation(co-IP).The co-IP results showed that PES1 could interact with ERα and ERβ by binding their 1~322aa region.Further experiments demonstrated that PES1 specifically inhibited the transactivation activity of ERβ in E2-independent manner by analyzing estrogen receptor element luciferase(ERE-LUC).These results suggested that PES1 may act as a new ER coregulator.Further mechanisms and roles in the ERβ signaling pathway and E2-induced neoplasms remain to be determined.