Posttranscriptional regulation of the c-myb proto-oncogene in estrogen receptor-positive breast cancer cells.
We have determined that expression of the c-myb proto-oncogene is associated with estrogen receptor (ER) status and not with tumor progression in human breast epithelial cells. Analysis of normal, immortalized, nontumorigenic, and tumorigenic mammary epithelial cells showed that only ER+ tumor cell lines expressed readily detectable levels of c-myb mRNA and a Mr 75,000 protein that was the same size as the c-myb transcripts and protein products present in hematopoietic cells. In this 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 protein expression was observed upon addition of beta-estradiol to the culture medium. Nuclear run-on transcription analyses showed that c-myb was transcribed at the same rate in the presence and absence of estrogen, suggesting that c-myb mRNA accumulation was regulated at a posttranscriptional level. To provide additional evidence that c-myb mRNA was dependent on ER expression, we examined c-myb mRNA levels in MCF-7 cells selected for resistance to antineoplastic drugs. c-myb expression was decreased only in cell lines that showed concomitant loss of ER expression. Moreover, c-myb mRNA was expressed and modulated by estrogen in ER-, MDA-MB-231 cells stably transfected with a human ER gene. When considered together, these data indicate that c-myb mRNA levels are regulated by estrogens and further suggest that this proto-oncogene plays a role in the biology of ER+ breast tumor cells.
Gudas
J M
JM
Medicine Branch, Division of Cancer Treatment, Medical Breast Cancer Section, National Cancer Institute, Bethesda, Maryland 20892, USA.
Klein
R C
RC
Oka
M
M
Cowan
K H
KH
D001940:Breast / Q000187:drug effects / Q000378:metabolism; D001943:Breast Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009857:Oncogenes; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D020598:Proto-Oncogene Proteins c-myb; D012323:RNA Processing, Post-Transcriptional; D011960:Receptors, Estrogen / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured; D020298:U937 Cells
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D011960:Receptors, Estrogen; D011994:Recombinant Proteins; D015534:Trans-Activators; D004958:Estradiol