Effect of protein tyrosine phosphatase 1B expression on transformation by the human neu oncogene.

Many oncogenes encode proteins with a tyrosine kinase activity that appears to be directly involved in the process of transformation. Because these kinases are themselves activated for transformation by tyrosine phosphorylation, proteins which remove phosphate from tyrosine residues, protein tyrosine phosphatases (also termed phosphotyrosine phosphatases and protein phosphotyrosyl phosphatases), are intuitive candidate transformation suppressors. The human PTP1B gene, previously cloned in our laboratory and encoding the low molecular weight protein tyrosine phosphatase PTPase 1B, was introduced into NIH 3T3 cells. Subsequent transformation of these PTPase 1B-expressing cells by an oncogenic form of the human neu gene was suppressed relative to control NIH 3T3 cells. This suppression of transformation was observed in assays for focus formation, anchorage-independent growth, and tumorigenicity. Tumorigenicity assays indicated a complex effect of PTPase 1B expression on transformation.