Growth-inhibitory effect of a streptococcal antitumor glycoprotein on human epidermoid carcinoma A431 cells: involvement of dephosphorylation of epidermal growth factor receptor.
An antitumor glycoprotein [streptococcal acidic glycoprotein (SAGP)] purified from an extract of Streptococcus pyogenes inhibited the growth of human epidermoid carcinoma A431 cells overexpressing epidermal growth factor receptor (EGFR) in a time- and a concentration-dependent manner. The antiproliferative effect of SAGP was diminished by preincubating the cells with pertussis toxin and by coadministration of sodium orthovanadate, an inhibitor of protein tyrosine phosphatases (PTPases). Western blot analysis showed that the immunoreactivity of a M(r) 170,000 band of cell lysate to antiphosphotyrosine antibody was reduced by SAGP, and the effect was abolished by sodium orthovanadate. The phosphotyrosine level of the precipitant with anti-EGFR antibody was reduced by SAGP, which was abolished by preincubation with pertussis toxin or by a coadministration with sodium orthovanadate. The PTPase activity transiently increased in the lysate of cells incubated with SAGP and was inhibitable by sodium orthovanadate. Additionally, preincubation of serum-starved A431 cells with SAGP decreased the epidermal growth factor-induced tyrosine phosphorylation of EGFR, and the effect of SAGP was sodium orthovanadate sensitive. These findings indicate that dephosphorylation of the M(r) 170,000 EGFR by activation of PTPase(s) may be responsible in part for the antiproliferative effect of SAGP on A431 cells.
Yoshida
J
J
Department of Pharmacology, Kanazawa Medical University, Ishikawa 920-0293, Japan. yayuyo@kanazawa-med.ac.jp
Ishibashi
T
T
Nishio
M
M
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001426:Bacterial Proteins; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D002374:Catalase / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006023:Glycoproteins / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D037342:Pertussis Toxin; D010766:Phosphorylation; D011233:Precipitin Tests; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D006023:Glycoproteins; D006131:Growth Inhibitors; C045283:SAGP protein, Streptococcus; D010566:Virulence Factors, Bordetella; D014638:Vanadates; D014443:Tyrosine; D004815:Epidermal Growth Factor; D002374:Catalase; D037342:Pertussis Toxin; D066246:ErbB Receptors; D017027:Protein Tyrosine Phosphatases; D019204:GTP-Binding Proteins