Regulation of c- myc expression by sodium butyrate in the colon carcinoma cell line Caco-2

Abstract

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.