Protein tyrosine phosphatase genes downregulated in melanoma

Phospho-tyrosine levels are increased in melanoma, apparently consistent wi th reports of elevated protein tyrosine kinase activity. Some protein tyros ine kinases are encoded by oncogenes and have been implicated in melanoma g enesis. Decreased protein tyrosine phosphatase activity may also increase p hospho-tyrosine. Protein tyrosine phosphatase genes are candidate tumor sup pressors and loss of expression may contribute to melanoma genesis. Here we survey protein tyrosine phosphatase expression in pigment cells. Protein t yrosine phosphatase genes were cloned by reverse transcriptase polymerase c hain reaction using degenerate primers based upon conserved sequences withi n the phosphatase catalytic domain. Reaction products were cloned and seque nced: 118 and 113 partial protein tyrosine phosphatase products were isolat ed from normal melanocytes and melanoma cells, respectively. Northern blott ing analysis was used to study expression of 15 protein tyrosine phosphatas e genes. Expression of PTP-kappa and PTP-pi was absent or downregulated in more than 20% of melanoma cell lines and in some unmanipulated melanoma bio psies. These closely related enzymes are members of the 2B receptor protein tyrosine phosphatase family previously implicated in contact inhibition. L oss of protein tyrosine phosphatase expression may contribute to the abnorm al tyrosine phosphorylation seen in melanoma; these genes are candidate tum or suppressors.