Interferon gamma-induced reduction in erbB-2 tyrosyl phosphorylation in human ovarian carcinoma cells.
Interferon, which inhibits growth of ovarian cancer cells in vivo and in vitro, decreases expression of erbB-2 protein in ovarian carcinoma cell lines. We now show that interferon-gamma (IFN-gamma) also decreases constitutive tyrosine phosphorylation of erbB-2 and inhibits erbB-2 kinase activity in an ovarian cancer cell line. SK-OV3 ovarian cancer cells, which over-express erbB-2, were treated with IFN-gamma for 0-72 hr. Immunoblot analysis revealed that IFN decreased the levels of tyrosyl phosphorylated erbB-2 24 hr after IFN treatment. Protein levels of erbB-2 were not changed until 72 hr post-treatment. Tyrosine kinase (TK) activity of immunoprecipitated erbB-2 for an exogenous substrate was decreased in IFN-treated cells. Total cellular protein tyrosine phosphatase (PTPase) activity for the epidermal growth factor receptor was not changed by IFN treatment. Our results suggest that the decreased levels of tyrosyl phosphorylated proteins observed after IFN treatment in SK-OV3 cells may be due to inhibition of erbB-2 kinase activity.
Mishra
S
S
University of Maryland Cancer Center, Baltimore 21201.
Hamburger
A W
AW
D002455:Cell Division / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases; D014407:Tumor Cells, Cultured
D066246:ErbB Receptors; D007371:Interferon-gamma; D017027:Protein Tyrosine Phosphatases; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases