Inhibition of transforming growth factor alpha (TGF-alpha)- mediated growth effects in ovarian cancer cell lines by a tyrosine kinase inhibitor ZM 252868

Simpson, B.J.B. et al. (1999) Inhibition of transforming growth factor alpha (TGF-alpha)- mediated growth effects in ovarian cancer cell lines by a tyrosine kinase inhibitor ZM 252868. British Journal of Cancer, 79(7-8), pp. 1098-1103. (doi: 10.1038/sj.bjc.6690175)

Abstract

The modulating effects of the epidermal growth factor (EGF) receptor-specific tyrosine kinase inhibitor ZM 252868 on cell growth and signalling have been evaluated in four ovarian carcinoma cell lines PE01, PE04, SKOV-3 and PE01(CDDP). Transforming growth factor alpha (TGF-alpha)-stimulated growth was completely inhibited by concentrations greater than or equal to 0.3 mu M in the PE01 and PE04 cell lines and by greater than or equal to 0.1 mu M in SKOV-3 cells. TGF-alpha inhibition or PE01(CDDP) growth was reversed by concentrations greater than or equal to 0.1 mu M ZM 252868. TGF-alpha- stimulated tyrosine phosphorylation of both the EGF receptor and c-erbB2 receptor in all four cell lines. The inhibitor ZM 252868, at concentrations greater than or equal to 0.3 mu M, completely inhibited TGF-alpha-stimulated tyrosine phosphorylation of the EGF receptor and reduced phosphorylation of the c-erbB2 protein. EGF-activated EGF receptor tyrosine kinase activity was completely inhibited by 3 mu M ZM 252868 in PE01, SKOV-3 and PE01(CDDP) cells. These data indicate that the EGF receptor-targeted TK inhibitor ZM 252868 can inhibit growth of ovarian carcinoma cells in vitro consistent with inhibition of tyrosine phosphorylation at the EGF receptor.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Leake, Prof Robin
• Authors: Simpson, B.J.B., Bartlett, J.M.S., Macleod, K.G., Rabiasz, G., Miller, E.P., Rae, A.L., Gordge, P., Leake, R.E., Miller, W.R., Smyth, J., and Langdon, S.P.
• Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer); R Medicine > RB Pathology
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: British Journal of Cancer
• ISSN: 0007-0920