Estrogenic G protein-coupled receptor 30 signaling is involved in regulation of endometrial carcinoma by promoting proliferation, invasion potential, and interleukin-6 secretion via the MEK/ERK mitogen-activated protein kinase pathway
Estrogenic G protein-coupled receptor 30 signaling is involved in regulation of endometrial carcinoma by promoting proliferation, invasion potential, and interleukin-6 secretion via the MEK/ERK mitogen-activated protein kinase pathway
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雌激素 G 蛋白偶联受体 30 信号传导通过 MEK/ERK 丝裂原激活蛋白激酶途径促进增殖、侵袭潜力和白细胞介素 6 分泌，从而参与子宫内膜癌的调节
DOI：
10.1111/j.1349-7006.2009.01148.x
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发表时间：
2009-06-01
期刊：
影响因子：
5.7
通讯作者：
Wan, Xiao-Ping
中科院分区：
文献类型：
--
作者：
He, Yin-Yan;Cai, Bin;Wan, Xiao-Ping
子宫内膜癌的调节机制和参与激素作用的信号转导通路尚不清楚。G蛋白偶联受体（GPR）30介导17 β-雌二醇（E2）的非基因组信号传导已变得明显。在此，我们发现GPR 30在子宫内膜癌组织和癌细胞系中高度表达，并正调控细胞增殖和侵袭。50例子宫内膜癌组织中检测到GPR 30的表达。GPR 30在子宫内膜癌组织中的转录水平显著高于正常子宫内膜组织（P < 0.05）。免疫组化结果显示，GPR 30蛋白在子宫内膜癌组织中的阳性表达率（35/50，70%）明显高于正常子宫内膜组织（8/30，26.67%）（χ 2 = 14.16，P = 0.0002）。GPR 30过表达与高级别子宫内膜癌相关。在两种人子宫内膜癌细胞系：RL 95 -2（雌激素受体阳性）和KLE（雌激素受体阴性）中也发现GPR 30表达。然后，在RL 95 -2和KLE细胞系中探索GPR 30在对E2和G1（一种非甾体GPR 30特异性激动剂）的增殖和侵袭反应中的作用。我们发现E2和G1可以启动这两种细胞系中的MAPK/ERK有丝分裂原活化蛋白激酶途径。此外，E2和G1通过GPR 30介导的MEK/ERK丝裂原活化蛋白激酶途径促进KLE和RL 95 -2增殖，刺激基质金属蛋白酶的产生和活性，以及增加白细胞介素-6的分泌。这些结果表明，GPR 30介导的非基因组信号可能在子宫内膜癌中发挥重要作用。（Cancer Sci 2009; 100：1051-1061）。
The regulatory mechanism of endometrial carcinoma and the signal transduction pathways involved in hormone action are poorly defined. It has become apparent that the G protein-coupled receptor (GPR) 30 mediates the non-genomic signaling of 17 beta-estradiol (E2). Here we show that GPR30 is highly expressed in endometrial cancer tissues and cancer cell lines and positively regulates cell proliferation and invasion. GPR30 expression was detected in 50 human endometrial carcinomas. The transcription level of GPR30 was significantly higher in the tissue of endometrial carcinoma than in normal endometrium (P < 0.05). Immunohistochemical assays revealed that the positive expression rate of GPR30 protein in endometrial carcinoma tissue (35/50, 70%) was statistically higher than in normal endometrium tissue (8/30, 26.67%) (chi(2) = 14.16, P = 0.0002). GPR30 overexpression was correlated with high-grade endometrial carcinoma. GPR30 expression was also found in two human endometrial cancer cell lines: RL95-2 (estrogen receptor positive) and KLE (estrogen receptor negative). The roles of GPR30 in proliferative and invasive responses to E2 and G1, a non-steroidal GPR30-specific agonist, in RL95-2 and KLE cell lines were then explored. We showed that E2 and G1 could initiate the MAPK/ERK mitogen-activated protein kinase pathway in both cell lines. What's more, E2 and G1 promoted KLE and RL95-2 proliferation and stimulated matrix metalloproteinase production and activity via the GPR30-mediated MEK/ERK mitogen-activated protein kinase pathway, as well as increased interleukin-6 secretion. These findings suggest that GPR30-mediated non-genomic signaling could play an important role in endometrial cancer. (Cancer Sci 2009; 100: 1051-1061).