Dopamine, by Acting through Its D2 Receptor, Inhibits Insulin-Like Growth Factor-I (IGF-I)-Induced Gastric Cancer Cell Proliferation via Up-Regulation of Kruppel-Like Factor 4 through Down-Regulation of IGF-IR and AKT Phosphorylation
Dopamine, by Acting through Its D2 Receptor, Inhibits Insulin-Like Growth Factor-I (IGF-I)-Induced Gastric Cancer Cell Proliferation via Up-Regulation of Kruppel-Like Factor 4 through Down-Regulation of IGF-IR and AKT Phosphorylation
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DOI：
10.2353/ajpath.2010.100617
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发表时间：
2010-12-01
影响因子：
6
通讯作者：
Basu, Sujit
中科院分区：
文献类型：
--
作者：
Ganguly, Subhalakshmi;Basu, Biswarup;Basu, Sujit
胰岛素样生长因子受体的过度I (IGF IR)和信号通路的激活的开发和发展发挥了关键作用胃癌伤寒肠神经递质多巴胺(DA)的一个主要报道有各种胃肠道的生理功能包括胃我们曾报道,DA和酪氨酸羟化酶速率限制酶的合成所需哒丢失恶性胃组织的影响损失的DA IGF IR诱导胃癌尚未阐明的增长所以我们研究DA的角色如果任何IGF IR诱导恶性胃细胞的增殖有显著增加磷酸化IGF IR的表达及其下游信号分子AICT在人类恶性胃组织与正常良性的组织进一步确定这损失达有任何影响IGF IR信号通路的激活恶性胃肿瘤体外实验使用AGS胃癌细胞进行我们的研究结果表明,DA代理通过d2受体抑制IGF我AGS细胞的诱导增殖细胞周期的调节KLF4负监管机构通过了IGF IR和一种蛋白激酶磷酸化的监管我们的研究结果表明,DA的IGF IR函数是一个重要的监管机构恶性胃癌细胞(分册2010 177DOI 10 2353/ajpath 2010 100617)
The overexpression of insulin like growth factor receptor I (IGF IR) and the activation of its signaling pathways both play critical roles in the development and progression of gastric cancer Dopamine (DA) a major enteric neurotransmitter has been reported to have a wide variety of physiological functions in the gastrointestinal tract including the stomach We have previously reported that both DA and tyrosine hydroxylase the rate limiting enzyme required for the synthesis of DA are lost in malignant gastric tissues The effect of this loss of DA on IGF IR induced growth of gastric cancer has not yet been elucidated we therefore investigated the role of DA if any on IGF IR induced proliferation of malignant gastric cells There was a significant increase in the expression of phosphorylated IGF IR and its downstream signaling molecule AICT in human malignant gastric tissues compared with normal nonmalignant tissues Furthermore to determine whether this loss of DA has any effect on the activation of IGF IR signaling pathways In malignant gastric tumors in vitro experiments were undertaken using AGS gastric cancer cells Our results demonstrated that DA acting through its D-2 receptor inhibits IGF I induced proliferation of AGS cells by up regulating KLF4 a negative regulator of the cell cycle through down regulation of IGF IR and AKT phosphorylation Our results suggest that DA is an important regulator of IGF IR function in malignant gastric cancer cells (Am J Pathol 2010 177 2701-2707 DOI 10 2353/ajpath 2010 100617)