Active PAI-1 expression reduces invasive breast, gynecologic cancer phenotypes.

2004 AUG 5 - (NewsRx.com & NewsRx.net) -- Active plasminogen activator inhibitor-1 expression reduces cell migration and invasion by breast and gynecologic cancer phenotypes, researchers report.

"Urokinase-type (uPA) plasminogen activator is regulated by serine protease inhibitors (serpins), especially plasminogen activator inhibitor-1 (PAI-1). In many cancers, uPA and PAI-1 contribute to the invasive phenotype," noted B.R. Whitley and colleagues at the University of North Carolina.

In their study, this team "examined the in vitro migration and invasive capabilities of breast, ovarian, endometrial and cervical cancer cell lines compared to their plasminogen activator system profiles. We then overexpressed active wild-type PAI-1 and an inactive 'substrate' P14 form of PAI-1 (T333R) using stable transfection and adenoviral gene delivery. We also upregulated endogenous uPA and PAI-1 in these cells by treatment with transforming growth factor-beta," they said.

Whitley and colleagues observed that "some breast and ovarian cancer cell lines with natural expression of uPA, PAI-1 and urokinase receptor showed substantial migration and invasion compared to other cell lines that lack expression of these proteins. However, overexpression of active wild-type PAI-1, but not P14-PAI-1 (T333R), in these cell lines showed reduced migration and invasion."

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