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Biochemistry (Moscow)

, Volume 73, Issue 7, pp 791–796 | Cite as

Implication of α5β1 integrin in invasion of drug-resistant MCF-7/ADR breast carcinoma cells: a role for MMP-2 collagenase

  • G. E. Morozevich
  • N. I. Kozlova
  • I. B. Cheglakov
  • N. A. Ushakova
  • M. E. Preobrazhenskaya
  • A. E. BermanEmail author
Article

Abstract

Expression of α5β1 integrin in the drug-resistant MCF-7/ADR breast carcinoma cells was inhibited by treatment of these cells with α5-specific siRNA. The decrease of α5β1 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 α5β1 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 α5β1 controls invasion ability of these cells by regulating expression of MMP-2, which involves PI-3K and Erk1/2 protein kinase signaling.

Key words

integrins signal protein kinases matrix proteases metastasis invasion 

Abbreviations

MMP

matrix-specific metalloproteinases

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Copyright information

© MAIK Nauka 2008

Authors and Affiliations

  • G. E. Morozevich
    • 1
  • N. I. Kozlova
    • 1
  • I. B. Cheglakov
    • 1
  • N. A. Ushakova
    • 1
  • M. E. Preobrazhenskaya
    • 1
  • A. E. Berman
    • 1
    Email author
  1. 1.Orekhovich Institute of Biomedical ChemistryRussian Academy of Medical SciencesMoscowRussia

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