Oncostatin M suppresses EGF-mediated protein tyrosine phosphorylation in breast cancer cells.
The effect of oncostatin M (OM) on epidermal growth factor (EGF)-mediated protein tyrosine phosphorylation in an infiltrating ductal breast carcinoma cell line, H3922, was investigated by Western blot analysis. Pretreatment of H3922 cells with OM for 72 h suppressed EGF-stimulated protein tyrosine phosphorylation signals by 77%. Interestingly, pretreatment with OM for 6 or 48 h had little effect on these signals. EGF-mediated tyrosine phosphorylation of EGF receptor (EGFR) was suppressed by 55% in 72-h OM pretreated H3922 cells. No reduction in EGFR protein expression was detected in these cells. Flow cytometric analysis verified that OM does not suppress EGFR expression. The effect of OM could not be attributed to induction of protein tyrosine phosphatases. An H3922 subclone cell line, designated H3922-8, was found to exhibit no proliferative response to treatment with EGF. However, EGF-mediated protein tyrosine phosphorylation was detected in these cells. Radioligand EGF binding studies comparing H3922 to H3922-8 cells indicated that the clonal cells apparently lack high affinity EGF receptors. The mechanism by which OM suppresses EGF-mediated tyrosine phosphorylation has not been completely characterized. However, the suppressive effect occurs regardless of whether the cells are acutely responsive (H3922) or virtually unresponsive (H3922-8) to EGF stimulation of cell growth.
Spence
M J
MJ
Department of Veterans Affairs Medical Center, Boise, ID 83702, USA. myexpense@aol.com
Vestal
R E
RE
Ma
Y
Y
Streiff
R
R
Liu
J
J
D001943:Breast Neoplasms / Q000276:immunology / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D066246:ErbB Receptors / Q000096:biosynthesis / Q000378:metabolism; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism* / Q000494:pharmacology; D053683:Oncostatin M; D010455:Peptides / Q000378:metabolism* / Q000494:pharmacology; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D003470:Culture Media; D016207:Cytokines; D018836:Inflammation Mediators; C508351:OSM protein, human; D010455:Peptides; D053683:Oncostatin M; D019000:Phosphotyrosine; D014443:Tyrosine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D017027:Protein Tyrosine Phosphatases