Stimulation of c-myc oncogene expression associated with estrogen-induced proliferation of human breast cancer cells.
Regulation of c-myc expression is known to be sensitive to a variety of mitogenic stimuli in various cell types. Since estrogen is a well documented mitogen of estrogen-responsive human breast cancer (HBC) cells, we studied the influence of estradiol and its antagonist tamoxifen on the expression of c-myc in HBC cell lines. Using Northern hybridization analysis, we monitored the accumulation of c-myc mRNA in a number of HBC cell lines. The cell lines studied included the estrogen-responsive, estrogen receptor positive (ER+) MCF-7, T-47D, the nonresponsive, estrogen receptor negative (ER-) MDA-MB-231, BT-20, and a nontumorous breast cell line, HBL-100. The effects of endogenous estrogen were minimized by culturing the cells in medium containing 10% (v/v) charcoal-treated fetal bovine serum and tamoxifen (10(-6) M) for 48 h prior to estradiol (10(-7) M) treatment. In the ER+ cell lines the addition of estradiol resulted in a noticeable increase in c-myc expression after 15 min with a maximal (greater than 10-fold) induction in 1-2 h. In the ER- cell lines the level of c-myc mRNA was high and was unaffected by estrogen or tamoxifen; in the ER- cancer cell lines, neither amplification nor rearrangement of the c-myc gene was observed. In contrast, the expression of another oncogene, c-H-ras, remained constant in both ER+ and ER- cell lines and was insensitive to estrogen and antiestrogen. These results suggest that regulation of c-myc expression may be an important step in estrogen-induced proliferation of HBC cells.
Dubik
D
D
Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Dembinski
T C
TC
Shiu
R P
RP
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002460:Cell Line; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D009693:Nucleic Acid Hybridization; D009857:Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D004967:Estrogens; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D013629:Tamoxifen; D004958:Estradiol