Variable expression of the transcription factors cAMP response element-binding protein and inducible cAMP early repressor in the normal adrenal cortex and in adrenocortical adenomas and carcinomas

The molecular mechanisms leading to adrenocortical tumorigenesis have been only partially elucidated so far. Because the pituitary hormone ACTH, via a ctivation of the CAMP pathway, regulates both cell proliferation/differenti ation and steroid synthesis in the adrenal cortex, in this study we focused on the CAMP-dependent transcription factors CAMP responsive element modula tor (CREM) and CAMP responsive element binding protein (CREB). We studied C REM and CREB expression by RT-PCR in human normal adrenal cortex (n 3), adr enocortical adenomas (n = 8), and carcinomas (n = 8). We found transcripts corresponding to the isoforms alpha, beta, gamma, and tau2 of the CREM gene in all of the normal adrenal tissues, in the adenomas, and in seven of eig ht carcinomas. On the other hand, mRNA for the inducible CAMP early repress or isoforms, which derive from an internal promoter of CREM gene, was detec ted in the normal adrenal and in seven of eight adenomas, but in only three of eight carcinomas. Similarly, CREB transcripts were readily detectable i n all normal adrenals and adenomas,. whereas they were not found in four of eight adrenal carcinomas. To further characterize the carcinomas, telomera se activity and the expression of the ACTH receptor gene were determined. T elomerase activity in the carcinomas resulted in levels significantly highe r than in the adenomas, whereas the levels of ACTH receptor mRNA were lower in the carcinomas. No correlation was found in the carcinomas between the levels of the ACTH receptor transcript and the loss of expression of CREB/i nducible CAMP early repressor, suggesting that this alteration is not secon dary to an upstream disregulation at the receptor level. In conclusion, our results suggest that an alteration in CAMP signaling may be associated wit h malignancies of the adrenal cortex.