Transcriptional regulation of c-myc oncogene expression by estrogen in hormone-responsive human breast cancer cells.
Enhanced c-myc oncogene expression associated with peptide mitogen-stimulated cell growth is primarily a result of a post-transcriptional event involving increased mRNA stability. We have recently shown that estradiol stimulates c-myc expression in estrogen receptor-positive human breast cancer cells. In this report, we show that in estrogen-responsive MCF-7 cells, estradiol stimulated the c-myc gene exclusively at the transcriptional level, increasing c-myc mRNA transcription more than 10-fold within 20 min, while having no effect on the c-myc mRNA half-life of 18 min. In addition, pretreatment of the cells with cycloheximide did not prevent induction of the c-myc oncogene, indicating a primary effect of estrogen. Furthermore, the elevated level of c-myc mRNA in estrogen-independent MDA-MB-231 cells was due primarily to a more stable c-myc mRNA with a half-life of 49 min, in the absence of enhanced transcription. These results indicate that different mechanisms of regulation of c-myc oncogene expression exist in hormone-dependent and -independent human breast cancer cells.
D001943:Breast Neoplasms / Q000235:genetics*; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000235:genetics; D003609:Dactinomycin / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006207:Half-Life; D006801:Humans; D009693:Nucleic Acid Hybridization; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D013629:Tamoxifen; D003609:Dactinomycin; D004958:Estradiol; D004247:DNA; D003513:Cycloheximide