Effects of Neuregulins on Invasion and Metastasis of Non-overexpression ErbB2 Breast Cancer Cells  

作　　者：Ya-mei Zhang Ting-ting Zhao Hua-yu Deng 

机构地区：[1]Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing 400016, China

出　　处：《Chinese Journal of Cancer Research》2009年第2期115-121,共7页中国癌症研究（英文版）

摘　　要：Objective： To explore the effects of neuregulins on ErbB2 receptor signal transduction pathway activation, and invasion and metastasis of non-overexpression ErbB2 breast cancer cell MDA-MB-231. Methods： The expressions of neuregulin were detected by immunocytochemistry and Western blot. MDA-MB-231 cells were treated with ErbB2 kinase inhibitor AG825. Proliferations were measured with MTT assay. Invasion and metastasis of MDA-ME-231 cells were evaluated with transwell chamber. The enzyme activities of MMP-2 and MMP-9 were detected by gelatin zymography. The expressions of MMP-2 and HIF-1α were detected by Western blot. Results： MDA-MB-231 cells expressed a relatively higher level of neuregulin. In Western blot, the positive reaction band was found at 44KD which coincides with the molecular weight of NRG. When MDA-MB-231 cells were treated with AG825, the proliferation was inhibited in a time-dose-dependent manner （P〈0.01）, invasion and metastasis were also depressed （P〈0.05）. The enzyme activities of MMP-2 and MMP-9 were lower （P〈0.05）. The expression levels of MMP-2 and HIF-lct were decreased （P〈0.05）. Conclusion： Our study indicates that neuregulins are synthesized in MDA-MB-231 cells as transmembrane proteins, neuregulins could activate ErbB2 receptor signal transduction pathway by autocrine or paracrine secretion, and induce invasion and metastasis of MDA-MB-231 cells.Objective： To explore the effects of neuregulins on ErbB2 receptor signal transduction pathway activation, and invasion and metastasis of non-overexpression ErbB2 breast cancer cell MDA-MB-231. Methods： The expressions of neuregulin were detected by immunocytochemistry and Western blot. MDA-MB-231 cells were treated with ErbB2 kinase inhibitor AG825. Proliferations were measured with MTT assay. Invasion and metastasis of MDA-ME-231 cells were evaluated with transwell chamber. The enzyme activities of MMP-2 and MMP-9 were detected by gelatin zymography. The expressions of MMP-2 and HIF-1α were detected by Western blot. Results： MDA-MB-231 cells expressed a relatively higher level of neuregulin. In Western blot, the positive reaction band was found at 44KD which coincides with the molecular weight of NRG. When MDA-MB-231 cells were treated with AG825, the proliferation was inhibited in a time-dose-dependent manner （P〈0.01）, invasion and metastasis were also depressed （P〈0.05）. The enzyme activities of MMP-2 and MMP-9 were lower （P〈0.05）. The expression levels of MMP-2 and HIF-lct were decreased （P〈0.05）. Conclusion： Our study indicates that neuregulins are synthesized in MDA-MB-231 cells as transmembrane proteins, neuregulins could activate ErbB2 receptor signal transduction pathway by autocrine or paracrine secretion, and induce invasion and metastasis of MDA-MB-231 cells.

关 键 词：Non-overexpression ErbB2 breast cancer NEUREGULINS Invasion Metastasis 

分 类 号：R737.9[医药卫生—肿瘤] R392-33[医药卫生—临床医学]