Overexpression of βPix-a in human breast cancer tissues

Pak interacting exchange factor (βPix) 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 βPix appear to play a critical role in the regulation of the cytoskeletal organization. The overexpression of βPix 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 βPix-a in human breast cancer tissues and adjacent normal tissues obtained from 39 breast cancer patients. Immunoblot analysis and RT-PCR revealed that βPix-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 βPix-a antibodies than normal tissues. βPix-a overexpression was inversely associated with extensive intraductal component (P<0.001). In conclusion, βPix-a expression was found to be higher in human breast cancer tissues than in normal breast tissues, which implies a role for βPix-a in human breast tumorigenesis. We suggest that βPix-a may be a useful marker of malignant disease in the breast.