Expression of protein tyrosine phosphatase alpha (RPTPα) in human breast cancer correlates with low tumor grade, and inhibits tumor cell growth in vitro and in vivo

Tyrosine phosphorylation is controlled by a balance of tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs), Whereas the contribution of PTKs to breast tumorigenesis is the subject of intense scrutiny, the potential role of PTPs is poorly known. RPTP alpha is implicated in the activation of Src family kinases, and regulation of integrin signaling, cell adhesion, and growth factor responsiveness. To explore its potential contribution to human neoplasia, we surveyed RPTPa protein levels in primary human breast cancer. We found RPTPa levels to vary widely among tumors, with 29% of cases manifesting significant overexpression, High RPTP alpha protein levels correlated significantly with low tumor grade and positive estrogen receptor status. Expression of RPTP alpha in breast carcinoma cells led to growth inhibition, associated with increased accumulation in G(0) and G(1), and delayed tumor growth and metastasis. To our knowledge, this is the first example of a study correlating expression level of a specific bona fide PTP with neoplastic disease status in humans.