Oncostatin M suppresses EGF-mediated protein tyrosine phosphorylation in breast cancer cells

The effect of oncostatin M (OM) on epidermal growth factor (EGF)-mediated p rotein tyrosine phosphorylation in an infiltrating ductal breast carcinoma cell line, H3922, was investigated by Western blot analysis. Pretreatment o f H3922 cells,vith OM for 72 h suppressed EGF-stimulated protein tyrosine p hosphorylation signals by 77%, Interestingly, pretreatment with OM for 6 or 48 h had little effect on these signals. EGF-mediated tyrosine phosphoryla tion of EGF receptor (EGFR) was suppressed by 55% in 72-h OM pretreated H39 22 cells. No reduction in EGFR protein expression was detected in these cel ls, Flow cytometric analysis verified that OM does not suppress EGFR expres sion, The effect of OM could not be attributed to induction of protein tyro sine phosphatases. An H3922 subclone cell line, designated H3922-8, was fou nd to exhibit no proliferative response to treatment with EGF. However, EGF -mediated protein tyrosine phosphorylation was detected in these cells. Rad ioligand EGF binding studies comparing H3922 to H3922-8 cells indicated tha t the clonal cells apparently lack high affinity EGF receptors, The mechani sm by which OM suppresses EGF-mediated tyrosine phosphorylation has not bee n completely characterized. However, the suppressive effect occurs regardle ss of whether the cells are acutely responsive (H3922) or virtually unrespo nsive (H3922-8) to EGF stimulation of cell growth. (C) 2000 Academic Press.