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 ent erocytic differentiation in culture. We used sodium butyrate to modify differentiation and growth properties of this cell line and considere d 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 but yrate reduces c-myc mRNA levels after a 30 min delay. Butyrate does no t affect c-myc expression at the level of transcriptional initiation o r elongation, as determined by run-on analysis, but at a post-transcri ptional 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 AR E is not modulated by butyrate or cycloheximide. These experiments sug gest that butyrate induces a factor involved in c-myc mRNA degradation that differs from the known ARE-associated proteins. Post-transcripti onal modification of gene expression could be one of the major targets for this anti-proliferative agent.