Overexpression of betaPix-a in human breast cancer tissues

Abstract

Pak interacting exchange factor (betaPix) is a recently cloned protein that contains a multidomain with many potential binding sites and is known to be involved in the regulation of Cdc42/Rac GTPases and Pak kinase activity. These domains of betaPix appear to play a critical role in the regulation of the cytoskeletal organization. The overexpression of betaPix enhances the activation of p38, which is thought to be an important downstream effector of the Rho GTPase family (Rac, Cdc42), which are involved in increased membrane ruffling and cell motility. This increase of cell mobility is an important feature of cancer invasion. We examined the expression of betaPix-a in human breast cancer tissues and adjacent normal tissues obtained from 39 breast cancer patients. Immunoblot analysis and RT-PCR revealed that betaPix-a expression was significantly increased in 37 of the 39 breast cancer tissues (94.9%) versus normal breast tissues. Immunohistochemical analysis showed that breast cancer tissues have consistently stronger immunoreactivity to betaPix-a antibodies than normal tissues. betaPix-a overexpression was inversely associated with extensive intraductal component (P<0.001). In conclusion, betaPix-a expression was found to be higher in human breast cancer tissues than in normal breast tissues, which implies a role for betaPix-a in human breast tumorigenesis. We suggest that betaPix-a may be a useful marker of malignant disease in the breast.