Protein tyrosine phosphorylation is a key regulator of cell growth regulation and, when aberrant, is linked with the process of oncogenic transformation. Since
tyrosine phosphatases (PTP) reverse phosphorylation mediated by
tyrosine kinases (PTK), it has been hypothesized, but insufficiently studied to date, that
PTPs function as
tumor suppressors. Alternatively,
PTPs may augment signal transduction by repriming substrates. To begin to assess the role of
PTPs in
ovarian cancer cell growth regulation, PTP partial cDNAs were cloned from the OVCA 433
ovarian cancer cell line using RT/PCR and degenerate
oligonucleotide primers for the PTP consensus domain. Thirteen partial cDNAs were isolated, the sequences of which, when compared to GenBank, suggested that they were derived from PTP family members. These included PTP-alpha, PTP-gamma, LAR, PTP-delta, T-cell PTP, PTP-2A(1D), PTP-1B, PTP-1C, PTP-H1,
PTP-PEST, PTP-Gallus, and two isolates which potentially represent novel
PTPs. Steady-state expression analyses revealed that PTP-1B expression was undetectable in normal epithelium but was expressed in four of five
ovarian cancer cell lines. In contrast, the expression of two SH2-containing
PTPs, PTP-1C and PTP-2A, was detected in the normal ovarian epithelium but lost from one or more
ovarian cancer cell lines. Finally, PTP-1B, PTP-alpha, and PTP-H1 expression was increased following HER-2/neu transfection of
ovarian cancer cell lines. These results suggest that both normal ovarian epithelial cells and
ovarian cancer cells express multiple
PTPs. Further, some
PTPs are differentially expressed between normal ovarian epithelium and
ovarian cancer cells. Intriguingly, the transfection and increased expression of the prognostically significant HER-2/neu PTK induced a selective increase in the expression of the PTP-alpha, PTP-1B, and PTP-H1
tyrosine phosphatases.