Department of Obstetrics and Gynecology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
J Cancer Res Clin Oncol. 2012 May;138(5):775-83. doi: 10.1007/s00432-011-1133-7. Epub 2012 Jan 24.
The mechanisms underlying the effects of estrogen on endometrial cancer remain undefined. Although the classical mechanism of the action of estrogen involves binding to the estrogen receptors α and β, and transduction of the signal into the cell, G protein-coupled receptor (GPR) 30 has been shown to mediate nongenomic estrogen signaling. The goal of this study was to determine the role of GPR30 signal in the basic process such as invasion and carcinogenesis of endometrial cancer.
We downregulated the expression of GPR30 in endometrial cancer cell line RL95-2 by transfection with shGPR30-pGFP-V-RS, a GPR30 antisense expression vector. The cells were then subjected to an MTT assay and a Transwell(®) migration assay. And an animal model was also used to investigate the influence of downregulation of GPR30 on oncogenesis.
Downregulation of GPR30 led to reduced growth and invasion by cells treated with 17β-estradiol. And the capacity of transfected RL95-2 cells to promote tumorigenesis was weakened in vivo.
Our data suggest that, for the endometrial cancer cell line RL95-2, GPR30 plays important roles in mediating the proliferative and invasive effects of estrogen and in tumorigenesis.
雌激素对子宫内膜癌影响的作用机制尚不清楚。虽然雌激素作用的经典机制涉及与雌激素受体 α 和 β 结合，并将信号转导到细胞内，但已表明 G 蛋白偶联受体 (GPR)30 介导非基因组雌激素信号。本研究的目的是确定 GPR30 信号在子宫内膜癌基本过程（如侵袭和癌变）中的作用。
通过用 shGPR30-pGFP-V-RS（GPR30 反义表达载体）转染 RL95-2 子宫内膜癌细胞系，下调 GPR30 的表达。然后将细胞进行 MTT 分析和 Transwell（®）迁移分析。还使用动物模型来研究下调 GPR30 对致癌作用的影响。
下调 GPR30 导致用 17β-雌二醇处理的细胞生长和侵袭减少。并且转染的 RL95-2 细胞在体内促进肿瘤发生的能力减弱。
我们的数据表明，对于子宫内膜癌细胞系 RL95-2，GPR30 在介导雌激素的增殖和侵袭作用以及肿瘤发生中起重要作用。
