The Role of RPTP-Alpha-Like Protein Tyrosine Phosphatases in Mammary Tumorigenesis

RPTPa is a protein tyrosine phosphatase implicated in the activation of Src family kinases, and in the regulation of integrin signaling, cell adhesion, and growth factor responsiveness, To explore its potential contribution to human neoplasia, we surveyed RPTPa protein levels in 51 primary breast cancer samples. We found RPTPa expression to vary widely among individual tumors, with significant overexpression occurring in approx. 27% of cases. RPTPa overexpression reflected reduced tumor aggressiveness, being strongly negatively correlated with tumor grade. In cell culture, expression of RPTPa in MCF-7 breast carcinoma cells led to growth inhibition, associated with increased accumulation in the G1 phase of the cell cycle. RPTPa expression also resulted in delayed tumor growth and metastasis in nude mice tumorigenicity as says. We propose that RPTPa overexpression in breast cancer constitutes a secondary response by which the cell attempts to maintain homeostasis perturbed during neoplastic transformation. To our knowledge, this is the first example of a study correlating expression level of a bona fide protein tyrosine phosphatase with neoplastic disease in humans.