The anti-proliferative effects of tyrosine kinase inhibitors towards tamoxifen-sensitive and tamoxifen-resistant human breast cancer cell lines in relation to the expression of epidermal growth factor receptors (EGF-R) and the inhibition of EGF-R tyrosine kinase

We have investigated the anti-proliferative effect of the tyrosine kinase inhibitors genistein, lavendustin A and 2,5-dihydromethylcinnimate (2,5-MeC) (a stable erbstatin analogue) against the epidermoid A431 cell line, the ZR-75-1 human breast cancer cell line and tamoxifen-resistant (ZR-75-9a1) and oestrogen-independent (ZR-PR-LT) variants. Increased EGF-R expression by ZR-75-9a1 was associated with decreased sensitivity to genistein and 2,5-MeC whilst decreased EGF-R expression (ZR-PR-LT) cells was associated with increased sensitivity to lavendustin A and 2,5-MeC. Anti-proliferative IC50 concentrations of 2,5-MeC, but not genistein or lavendustin A, inhibited EGFR-R associated tyrosine kinase activity of ZR-75-1 cells and variants by 20-50%, (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.