CYCLIC-AMP DOWN-REGULATES C-MYC EXPRESSION BY INHIBITION OF TRANSCRIPT INITIATION IN HUMAN B-PRECURSOR REH CELLS

In the human pre-B cell line Reh, activation of the cyclic AMP signal transduction pathway induces a rapid, transient 10-fold down-regulation of steady-state c-myc mRNA. We have investigated the mechanisms involved in this cAMP-mediated regulation of c-myc expression. Forskolin did not alter c-myc mRNA stability. Initiation of c-myc transcripts was strongly inhibited after 1 h of forskolin treatment, as measured by nuclear run-on assays. Reinitiation of c-myc transcription was apparent after 3-4 h, and full transcriptional elongation was detected after 8 h of forskolin treatment. These data suggest that cyclic AMP downregulates c-myc expression by inhibition of transcriptional initiation.