Transcriptional activation of c-myc proto-oncogene by estrogen in human ovarian cancer cells.
NIH:OVCAR-3 is a human ovarian cancer cell line that expresses a moderate amount of estrogen receptors, 28 fmol/mg protein. We have found that estrogen at a concentration of 10(-7) M induced a 2.3-fold increase in the growth of NIH:OVCAR-3 cells after 48 h stimulation. A 4-fold increase in c-myc mRNA expression at 30 min and a 7.5-fold increase at 50 min post-induction with estradiol were observed. Nuclear run-on analysis indicated that c-myc transcripts increased 4-fold within 10 min of estrogen addition. The half-life of c-myc mRNA was 64 min +/- 5 min and was not affected by estrogen. Antisense oligonucleotide to c-myc specifically inhibited the estrogen stimulated c-myc protein expression as well as the growth of NIH:OVCAR-3 cells. A control ovarian cancer cell line OC-3-VGH that had few estrogen receptors (1 fmol/mg protein) did not respond to estrogen in growth; however, these cells respond to estrogen with a 1.5-fold increase in c-myc mRNA. The stability of c-myc mRNA of these cells was not affected by estrogen. Our results indicate that transcriptional induction of c-myc expression by estrogen plays a critical role in the proliferation of NIH:OVCAR-3 cells.
Chien
C H
CH
Department and Institute of Biochemistry, National Yang-Ming Medical College, Shih Pai, Taipei, Taiwan.
Wang
F F
FF
Hamilton
T C
TC
D002455:Cell Division / Q000187:drug effects; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000473:pathology; D016373:DNA, Antisense / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016259:Genes, myc / Q000187:drug effects*; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D000090063:Proto-Oncogene Mas; D011960:Receptors, Estrogen / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D016373:DNA, Antisense; C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D000090063:Proto-Oncogene Mas; D011960:Receptors, Estrogen; D013629:Tamoxifen; D015735:Mifepristone; D004958:Estradiol