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

FEBS Lett. 1993 Jul 12;326(1-3):45-50. doi: 10.1016/0014-5793(93)81758-r.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Northern
  • Butyrates / pharmacology*
  • Butyric Acid
  • Cell Differentiation / drug effects
  • Cell Division / drug effects
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology
  • Cycloheximide / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Genes, myc / genetics*
  • Half-Life
  • Humans
  • Nucleic Acid Hybridization
  • RNA, Messenger / metabolism
  • Tumor Cells, Cultured


  • Butyrates
  • RNA, Messenger
  • Butyric Acid
  • Cycloheximide