Effects of steroid hormones and peptide growth factors on protooncogene c-fos expression in human breast cancer cells.
To investigate if the estrogen control of the tumorigenic phenotype of breast cancer cells was mediated through activation of the c-fos protooncogene, we examined the expression of this oncogene in MCF-7 cells. In cells synchronized by double thymidine blockade, the peptide growth factors transforming growth factor alpha and epidermal growth factor increased c-fos mRNA levels 6-fold above controls after 30 min of treatment. The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, increased c-fos mRNA levels 4- to 5-fold above control. 17 beta-Estradiol, a growth stimulator, increased c-fos mRNA levels less than 2-fold above control levels, while progesterone, vitamin D3, dihydrotestosterone, and dexamethasone had little effect on c-fos mRNA levels. In contrast, 17 beta-estradiol treatment initially diminished the c-myc RNA level after 30 min of treatment and resulted in an elevation of c-myc by 2.5 h after initiation of treatment. We conclude that c-fos induction in these cells is growth related and accompanies stimulation by transforming growth factor alpha and epidermal growth factor. 17 beta-Estradiol, on the other hand, induced much smaller increases in c-fos mRNA levels, suggesting an alternative or more complex mechanism of cellular stimulation.
Wilding
G
G
Medicine Branch, National Cancer Institute, Bethesda, Maryland 20878.
Lippman
M E
ME
Gelmann
E P
EP
D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D010455:Peptides / Q000494:pharmacology*; D011374:Progesterone / Q000494:pharmacology*; D011519:Proto-Oncogenes / Q000187:drug effects*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*; D015291:Transforming Growth Factors
D006133:Growth Substances; D010455:Peptides; D012333:RNA, Messenger; D011374:Progesterone; D004958:Estradiol; D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D003907:Dexamethasone; D013755:Tetradecanoylphorbol Acetate