Oncostatin M-mediated transcriptional suppression of the c-myc gene in breast cancer cells.
Oncostatin M (OM) inhibits proliferation of H3922, a human breast cancer cell line derived from a ductal infiltrating carcinoma. We have found that treatment of H3922 cells with OM for 72 h lowers the steady-state level of c-myc mRNA to 16% of that seen in control cells. Our present study showed that down-regulation of c-myc mRNA levels was both dose and time dependent. Results from nuclear run-off analysis and mRNA stability studies established that a major component of the observed OM-induced down-regulation of c-myc mRNA occurs at the transcriptional level. OM treatment of H3922 cells reduced the abundance of actively transcribed c-myc mRNAs to approximately 25% of that observed in control cells. These data were supported by our finding that OM did not significantly affect the half-life of c-myc mRNA in actinomycin-treated H3922 cells. Taken together, these data demonstrate that the suppressive effect of OM on c-myc gene expression in H3922 cells occurs at the transcriptional level.
Spence
M J
MJ
Veterans Affairs Medical Center, Boise, Idaho 83702, USA.
Vestal
R E
RE
Liu
J
J
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics*; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D006801:Humans; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D019384:Nucleic Acid Synthesis Inhibitors; C508351:OSM protein, human; D010455:Peptides; D012333:RNA, Messenger; D053683:Oncostatin M; D003609:Dactinomycin