C-MYC EXPRESSION IS CONTROLLED BY THE MITOGENIC CAMP-CASCADE IN THYROCYTES

In dog thyroid epithelial cells in primary culture, thyrotropin (TSH), acting through cAMP, induces proliferation and differentiation expres sion, whereas epidermal growth factor (EGF) and phorbol esters induce proliferation and dedifferentiation. In these cells, we have detailed the regulation by cAMP of the c-myc protooncogene mRNA and protein. Th e cAMP signaling pathway induces a biphasic increase of c-myc mRNA and protein. c-Myc protein accumulation follows the abundance and kinetic s of its mRNA expression. Using in vitro elongation of nascent transcr ipts to measure transcription and actinomycin D (AcD) chase experiment s to study mRNA stability, we have shown that in the first phase cAMP releases a transcriptional elongation block. No modification of transc riptional initiation was observed. After 30 min of treatment with TSH, c-myc mRNA was also stabilized. During the second phase, cAMP stabili zation of the mRNA disappears and transcription is again shutt off. Th us, in a tissue in which it stimulates proliferation and specific gene expression, cAMP regulates biphasically c-myc expression by mechanism s operating at the transcriptional and posttranscriptional levels. (C) 1996 Wiley-Liss, Inc.