Gab2 effects the invasion and metastasis of breast carcinoma through PI3 K/Akt/ARK5/MMP signal pathway / 中国药理学通报

ABSTRACT

Aim To investigate the molecular mecha-nism of Gab2 in the invasion and metastasis of breast cancer and provide a theoretical basis for clinical pre-vention of breast cancer invasion and metastasis. Methods The Gab2 , MMP-2 and MMP-9 expressions in 80 cases of breast cancer were detected by immuno-histochemistry . Western blot was used to detect the ex-pression of Gab2 protein in MDA-MB-231 cells and MCF-7 cells. The siRNA plasmid was used to transfect MDA-MB-231 cells. Western blot was used to detect the proteins expression of Gab2 , MMP-2 and MMP-9 . Transwell in vitro experiment was used to detect the in-vasion ability of each group transfected MDA-MB-231 cells, Western blot was used to analyze phosphorylation of Akt and ARK5 induced by epithelial growth factor ( EGF ) in transfected cells ( SiGab2/MDA-MB-231 and Scr/MDA-MB-231 ) . Results The expression of Gab2 protein in invasive ductal carcinoma was signifi-cantly higher than in normal breast tissue ( P<0. 01 ) . The expression of Gab2 was dramatically correlated with lymph node metastasis, ER expression, tumor his-tological grade, MMP-2 and MMP-9 (P<0. 05). The expression of Gab2 protein in MDA-MB-231 cells was higher than in MCF-7 cells. The expression of Gab2, MMP-2 and MMP-9 decreased in SiGab2/MDA-MB-231 cells and the invasion ability of SiGab2/MDA-MB-231 cells was significantly decreased ( P<0. 05 ) , and after 5 minutes’ stimulating by EGF, the phosphoryla-tion of Akt and ARK5 was significantly reduced. Con-clusion Gab2 can promote the invasion and metasta-sis of breast cancer by effecting the expression of MMP-2 and MMP-9 through PI3 K/ Akt /ARK5 signal path-way.