Differential sensitivity of MCF-7 and LCC2 cells, to multiple growth inhibitory agents: possible relation to high bcl-2/bax ratio?

Comparison of LCC2, the E-2-independent, tamoxifen-resistant subline of the MCF-7 human breast cancer cell line with its parent line, disclosed that i t is more resistant to growth inhibition and apoptosis induction by a varie ty of agents acting by diverse mechanisms. Thus, LCC2 cells can serve as a useful in-vitro model for the study of the molecular mechanisms of this res istance. It was found that bcl-2 protein and mRNA were elevated and that ba x protein and mRNA were reduced in LCC2-compared with MCF-7 cells. Incubati on of both lines in the presence of bcl-2 antisense caused growth inhibitio n and reduced bcl-2 protein levels only in MCF-7 cells, suggesting the invo lvement of bcl-2 in the regulation of normal growth of breast cancer cells. Increased bcl-2 expression in breast cancer cells may correlate with their resistance to growth inhibitory agents. Bcl-2 is a useful target for enhan cing the effects of growth inhibitory agents. (C) 2000 Elsevier Science Ire land Ltd. All rights reserved.