Implication of alpha₅beta₁ Integrin in Invasion of Drug-Resistant MCF-7/ADR Breast Carcinoma Cells: a Role for MMP-2 Collagenase

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G. E. Morozevich, N. I. Kozlova, I. B. Cheglakov, N. A. Ushakova, M. E. Preobrazhenskaya, and A. E. Berman^*

Orekhovich Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, ul. Pogodinskaya 10, 119121 Moscow, Russia; fax: (495) 245-0857; E-mail: berman@ibmc.msk.ru; AlbertBerman@rambler.ru

^* To whom correspondence should be addressed.

Received December 18, 2007; Revision received February 20, 2008

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Expression of alpha₅beta₁ integrin in the drug-resistant MCF-7/ADR breast carcinoma cells was inhibited by treatment of these cells with alpha₅-specific siRNA. The decrease of alpha₅beta₁ expression resulted in a sharp decrease of expression of MMP-2 collagenase and inhibition of invasion activity of these cells in vitro. Similar decrease of invasion was also observed during inhibition of MMP-2 expression by treatment of these cells with MMP-2-specific siRNA. Inhibition of alpha₅beta₁ expression was also accompanied by significant decrease in cell content of active (phosphorylated) forms of signal protein kinases Akt and Erk1/2. Inhibition of activity of these kinases by treatment of cells with PI-3K/Akt-specific inhibitor LY294002 or Erk-specific inhibitor PD98059 resulted in inhibition of MMP-2 expression and the decrease of invasion in vitro. These data suggest that alpha₅beta₁ controls invasion ability of these cells by regulating expression of MMP-2, which involves PI-3K and Erk1/2 protein kinase signaling.

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KEY WORDS: integrins, signal protein kinases, matrix proteases, metastasis, invasion

DOI: 10.1134/S0006297908070079

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