Inhibition of stimulus‐dependent epidermal growth factor receptor and transforming growth factor‐α mRNA accumulation by the protein kinase C inhibitor staurosporine

FEBS Letters

Paterson, Andrew J.¹  Kudlow, Jeffrey E.¹  Bjorge, Jeffrey D.¹  Mills, Gordon B.² 

[1] Departments of Clinical Biochemistry and Medicine, Banting and Best Diabetes Centre, Toronto General Hospital, University of Toronto, Toronto, Ontario M5G 1L5, Canada;Oncology Research, Toronto General Hospital, University of Toronto, Toronto, Ontario M5G 1L5, Canada

关键词: Growth factor receptor;    Protein kinase C;    Tumor promotor;    Phorbol ester;   

DOI  :  10.1016/0014-5793(89)80171-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The ability of staurosporine, a potent inhibitor of protein kinase C, to block certain cellular events initiated by 12-O-tetradecanoylphorbol-13-acetate (TPA) and epidermal growth factor (EGF) was examined. Treatment of MDA468 breast cancer cells with TPA decreases EGF binding to the cell surface and this effect is blocked by pretreatment with staurosporine with an IC₅₀ of 30 nM. Either 10⁻⁹ M EGF or 100 ng/ml TPA stimulated the accumulation of both EGF receptor and TGF-α mRNA and staurosporine (50 nM) completely abolished these mRNA accumulations. Staurosporine did not block EGF-stimulated tyrosine phosphorylation of its receptor as measured by immunoblotting with anti-phos-photyrosine antibodies. The ability of staurosporine to block the mRNA responses of either EGF or TPA suggests that these two agents have common signaling pathways and it implies a role for protein kinase C in the control of EGF receptor and TGF-α expression.

【 授权许可】

Unknown