Regulation of c-myc expression by sodium butyrate in the colon carcinoma cell line Caco-2.
The human colon carcinoma cell line Caco-2 spontaneously undergoes enterocytic differentiation in culture. We used sodium butyrate to modify differentiation and growth properties of this cell line and considered c-myc expression as a potential target. Degradation of normal c-myc mRNAs with a half-life of 20 min is not coupled to translation in this cell line, as determined by cycloheximide treatment. We show that butyrate reduces c-myc mRNA levels after a 30 min delay. Butyrate does not affect c-myc expression at the level of transcriptional initiation or elongation, as determined by run-on analysis, but at a post-transcriptional level. Cycloheximide blocks butyrate-dependent reduction of c-myc mRNA levels. Cross-linking experiments show that a 34 kDa protein binds specifically to the c-myc AU-rich instability determinant found in the 3'-untranslated region (ARE). Binding of this protein to the ARE is not modulated by butyrate or cycloheximide. These experiments suggest that butyrate induces a factor involved in c-myc mRNA degradation that differs from the known ARE-associated proteins. Post-transcriptional modification of gene expression could be one of the major targets for this anti-proliferative agent.
Souleimani
A
A
Département d'anatomie et de biologie cellulaire, Faculté de Médecine, Université de Sherbrooke, Québec, Canada.
Asselin
C
C
D015152:Blotting, Northern; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D003513:Cycloheximide / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016259:Genes, myc / Q000235:genetics*; D006207:Half-Life; D006801:Humans; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured
D002087:Butyrates; D012333:RNA, Messenger; D020148:Butyric Acid; D003513:Cycloheximide