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首页> 外文期刊>Biochemical and Biophysical Research Communications >Involvement of membrane-type bile acid receptor M-BAR/TGR5 in bile acid-induced activation of epidermal growth factor receptor and mitogen-activated protein kinases in gastric carcinoma cells.
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Involvement of membrane-type bile acid receptor M-BAR/TGR5 in bile acid-induced activation of epidermal growth factor receptor and mitogen-activated protein kinases in gastric carcinoma cells.

机译:膜型胆汁酸受体M-BAR / TGR5参与胆汁酸诱导的胃癌细胞中表皮生长因子受体和丝裂原活化蛋白激酶的活化。

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摘要

Bile acids, which have been implicated in gastrointestinal-tract cell carcinogenesis, share properties with tumor promoters in that both affect signal transduction pathways responsible for cell proliferation and apoptosis. In the present study, we demonstrate that EGFR-ERK1/2 is activated following treatment of AGS human gastric carcinoma cells with bile acids. EGFR phosphoactivation is ligand-dependent, since treatment of cells with HB-EGF antisera or CM197 (a selective inhibitor of HB-EGF) markedly inhibits deoxycholate (DC)-promoted activation. Membrane-type bile acid receptor (M-BAR)/TGR5 is a recently identified G-protein-coupled receptor (GPCR). In AGS cells, siRNAs that target M-BAR suppress DC-induced phosphorylation of EGFR. Furthermore, introduction of siRNAs targeting ADAM17 transcripts resulted in suppression of DC-induced activation of EGFR and ERK1/2. These results suggest that in AGS cells, DC transactivates EGFR through M-BAR- and ADAM/HB-EGF-dependent mechanisms.
机译:胆汁酸与胃肠道细胞癌变有关,它与肿瘤启动子具有共同的特性,因为它们都影响负责细胞增殖和凋亡的信号转导途径。在本研究中,我们证明在用胆汁酸治疗AGS人胃癌细胞后,EGFR-ERK1 / 2被激活。 EGFR磷酸化激活依赖于配体,因为用HB-EGF抗血清或CM197(HB-EGF的选择性抑制剂)处理细胞可显着抑制脱氧胆酸盐(DC)促进的激活。膜型胆汁酸受体(M-BAR)/ TGR5是最近发现的G蛋白偶联受体(GPCR)。在AGS细胞中,靶向M-BAR的siRNA抑制DC诱导的EGFR磷酸化。此外,针对ADAM17转录本的siRNA的引入导致抑制DC诱导的EGFR和ERK1 / 2激活。这些结果表明,在AGS细胞中,DC通过M-BAR和ADAM / HB-EGF依赖性机制使EGFR活化。

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