Regulation of C-fos expression by sodium butyrate in the human colon carcinoma cell line Caco-2.

We used sodium butyrate to modify the differentiation and growth properties of the Caco-2 colon adenocarcinoma cell line and considered c-fos proto-oncogene expression as a potential target. C-fos is induced by butyric acid very rapidly at a post-transcriptional level and is stimulated transcriptionally at later times. This transcriptional induction does not result in an increase in steady-state mRNA levels. We show by transient transfection assays that the ATF-CRE binding site located between -63 and -54 relative to the c-fos transcriptional start site is a target for butyrate-induced fos transcription. Furthermore, gel retardation assays show an increase in CRE binding activity in cells treated with butyrate. These results demonstrate that butyrate can affect specific transcription factors important for cell growth and differentiation at multiple levels of regulation.