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In this study, we show that normal human epithelial ovarian cell line, HOSE, and ovarian cancer cell lines, OVCA 429, OVCA 433, and OVHS\u20101, expressed \u03b1v integrin and associated \u03b21, \u03b23, and \u03b25 subunits, but only ovarian cancer cell lines OVCA 429 and OVCA 433 expressed \u03b1v\u03b26 integrin. The expression of \u03b1v\u03b26 in OVCA 429 and OVCA 433 was far higher than \u03b1v\u03b23 and \u03b1v\u03b25 integrin and correlated with high p42\/p44 mitogen activated protein kinase (MAPK) activity and high secretion of high molecular weight urokinase plasminogen activator (HMW\u2010uPA), pro\u2010metalloproteinase 2 and 9 (pro\u2010MMP\u20109 and pro\u2010MMP\u20102). In contrast to HOSE and OVHS 1, OVCA 433 and OVCA 429 exhibited approximately 2\u2010fold more plasminogen\u2010dependent [<jats:sup>3<\/jats:sup>H]\u2010collagen type IV degradation. Plasminogen\u2010dependent [<jats:sup>3<\/jats:sup>H]\u2010collagen IV degradation was inhibited by inhibitor of uPA (amiloride) and MMP (phenanthroline) and by antibodies against uPA or MMP\u20109 or \u03b1v\u03b26 integrin, indicating the involvement of \u03b1v\u03b26 integrin, uPA and MMP\u20109 in the process. The \u03b1v\u03b26 correlated increase in HMW\u2010uPA and pro\u2010MMP secretion could be inhibited by tyrosine kinase inhibitor genistein or the MEK 1 inhibitor U0126, consistent with a role of active p42\/44 MAPK in the elevation of uPA, MMP\u20109, and MMP\u20102 secretion. Under similar conditions, genistein and U0126 inhibited plasminogen\u2010dependent [<jats:sup>3<\/jats:sup>H]\u2010collagen type IV degradation. These data suggest that sustained elevation of p42\/44 MAPK activity may be required for the co\u2010expression of \u03b1v\u03b26 integrin, which in turn may regulate the malignant potential of ovarian cancer cells via proteolytic mechanisms. J. Cell. Biochem. 84: 675\u2013686, 2002. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.10080","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T22:17:27Z","timestamp":1030313847000},"page":"675-686","source":"Crossref","is-referenced-by-count":46,"title":["Association between \u03b1v\u03b26 integrin expression, elevated p42\/44 kDa MAPK, and plasminogen\u2010dependent matrix degradation in ovarian 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