POSTTRANSCRIPTIONAL REGULATION OF THE C-MYB PROTOONCOGENE IN ESTROGENRECEPTOR-POSITIVE BREAST-CANCER CELLS

We have determined that expression of the c-myb protooncogene is assoc iated with estrogen receptor (ER) status and not with tumor progressio n in human breast epithelial cells, Analysis of normal, immortalized, nontumorigenic, and tumorigenic mammary epithelial cells showed that o nly ER(+) tumor cell lines expressed readily detectable levels of c-my b mRNA and a M(r) 75,000 protein that was the same size as the c-myb t ranscripts and protein products present in hematopoietic cells, In thi s report we show that c-myb mRNA and protein levels are down-regulated during estrogen withdrawal. A 20-fold increase in c-myb mRNA and prot ein expression was observed upon addition of beta-estradiol to the cul ture medium, Nuclear run on transcription analyses showed that c-myb w as transcribed at the same rate in the presence and absence of estroge n, suggesting that c-myb mRNA accumulation was regulated at a posttran scriptional level, To provide additional evidence that c-myb mRNA was dependent on ER expression, we examined c-myb mRNA levels in MCF-7 cel ls selected for resistance to antineoplastic drugs, c-myb expression w as decreased only in cell lines that showed concomitant loss of ER exp ression, Moreover, c-myb mRNA was expressed and modulated by estrogen in ER(-), MDA-MB-231 cells stably transfected with a human ER gene, Wh en considered together, these data indicate that c-myb mRNA levels are regulated by estrogens and further suggest that this proto-oncogene p lays a role in the biology of ER(+) breast tumor cells.