Regulation of human calcitonin gene transcription by cyclic AMP.

Transcription of the human calcitonin (CT) gene is markedly increased by cAMP in the TT line of medullary thyroid carcinoma. This response is conferred by 5' flanking DNA sequences located between -132 and -252 relative to the transcription initiation site. Within this region are an upstream cyclic AMP response element (CRE), a downstream CRE flanked by two octamer motifs, and two adjacent C-rich AP2-like sequences. In transfection experiments in TT cells, the downstream CRE, combined with CT promoter sequences, generated 70% of the maximal cAMP response. The upstream CRE and the C-rich elements conferred 10 and 30% of this response, respectively. In gel mobility shift assays, specific TT cell proteins bound to each of these sequences. Therefore, the cAMP response of the CT gene is complex, requiring multiple elements acting in concert.