IMPLICATION OF α<sub>5</sub>β<sub>1</sub> INTEGRIN IN INVASION OF DRUG-RESISTANT MCF-7/ADR BREAST CARCINOMA CELLS: A ROLE FOR MMP-2 COLLAGENASE
In a drug-resistant MCF-7/ADR breast carcinoma cell line, down-regulation of α<sub>5</sub>β<sub>1</sub> integrin by a α<sub>5</sub>-specific siRNA markedly decreased the expression of MMP-2 collagenase and inhibited an <i>in vitro </i>invasion of the cells in matrigel. Similar reduction in invasive activity resulted from silencing the MMP-2 collagenase caused by a MMP-2-specific siRNA. Down-regulation of α<sub>5</sub>β<sub>1</sub> was accompanied by a markedly reduced expression of active (phosphorylated) forms of Akt and Erk1/2 kinases. Inhibition of these kinases by an Akt-specific compound LY294002 or a Erk-specific PD98059 substantially reduced the expression of MMP-2 and decreased the cell invasive activity. These results suggested that in the breast carcinoma cells, acquired drug-resistance, α<sub>5</sub>β<sub>1</sub> integrin is involved in cell invasion through controlling MMP-2 expression by recruitment of PI-3K/Akt and Erk signaling pathways.