Expression and Regulation of the Retinoic Acid Receptor Beta Gene in HumanMammary Epithelial Cells

摘要

We have performed BetaRARE gel shift analyses and partial RARB promoter sequenceanalysis for 4 and 5 breast cancer cell lines, respectively. We have introduced a functional RARBeta gene into four breast cancer cell lines by retroviral vector mediated transduction. We have analyzed 24 differential niRNA transcripts from the cell line, MCF7 cultured in the presence of retinoic acid. We have initiated studies to determine RARB expression in primary tumors. Tumor cells exhibit a dramatically more complex binding to the promoter response element, RARE for all tumor lines tested to date (n=3) compared to normal mammary epithelial cells. We have found 2 mutations in the promoter of the cell line, MDA-MB-23 1. We show that reconstitution of an expressed RARB gene results in dramatic growth suppression of breast cell lines: MCF7 and MDA-MB-23 1, with induction of apoptosis in the MCF7 cells when they are cultured with retinoic acid. Our findings continue to support the hypothesis that the RARB gene product is a candidate tumor suppressor gene for breast cancer.