The effects of β-estradiol on raf activity, cell cycle progression and growth factor synthesis in the MCF-7 breast cancer cell line

Abstract

The aim of this study was to test the hypothesis that some of the proliferative effects of steroid hormones on cancer cells are mediated by the Raf proto-oncogenes. The human breast cancer cell line MCF-7 is estrogen-receptor (ER) positive (+). NCI/ADR-RES is a human cell line lacking the estrogen receptor (ER-) that was initially named MCF-ADR. Raf-1, A-Raf and B-Raf kinase activities were examined in cell lines treated with β-estradiol for 24 hours. Increases in Raf-1 and A-Raf activities were observed after treatment with β-estradiol in the ER (+) MCF-7 cells but not in the ER (-) NCI/ADR-RES cells. In contrast, no significant changes in B-Raf activity were observed. Thus β-estradiol can induce Raf-1 and A-Raf activities in ER (+) cells. In addition, β-estradiol caused cell cycle progression in MCF-7 cells and an increased proliferative response to β-estradiol was observed in MCF-7, which overexpressed constitutively- active Raf-1 (MCF/ΔRaf-1). Increased mRNA levels of the ligand for the c-erb-B2 receptor, amphiregulin (ARG) were observed after β-estradiol treatment of MCF-7 cells whereas constitutively higher levels of ARG and its receptor, c-erb-B2 mRNAs were detected in MCF/ΔRaf-1 cells. These findings suggest that targeting Raf may prove efficacious in breast cancer therapies. ©2002 Landes Bioscience.