This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Peri, A. Articles by Mannelli, M. Search for Related Content PubMed PubMed Citation Articles by Peri, A. Articles by Mannelli, M.

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

Endocrine Unit (A.P., P.L., B.C., F.C., C.C., P.F., M.S., M.M.), Medical Genetics Unit (S.B.-P.), and Clinical Biochemistry Unit (S.G.), Department of Clinical Physiopathology, University of Florence, 50139 Florence, Italy; Department of Human Pathology and Oncology (G.N.), University of Florence, 50139 Florence, Italy; Department of Internal Medicine (G.A.), University of Ancona, 60131 Ancona, Italy; and Department of Medical and Surgical Sciences (F.M.), University of Padova, 35131 Padova, Italy

Abstract

The molecular mechanisms leading to adrenocortical tumorigenesis have been only partially elucidated so far. Because the pituitary hormone ACTH, via activation of the cAMP pathway, regulates both cell proliferation/differentiation and steroid synthesis in the adrenal cortex, in this study we focused on the cAMP-dependent transcription factors cAMP responsive element modulator (CREM) and cAMP responsive element binding protein (CREB). We studied CREM and CREB expression by RT-PCR in human normal adrenal cortex (n = 3), adrenocortical adenomas (n = 8), and carcinomas (n = 8). We found transcripts corresponding to the isoforms , ß, , and 2 of the CREM gene in all of the normal adrenal tissues, in the adenomas, and in seven of eight carcinomas. On the other hand, mRNA for the inducible cAMP early repressor isoforms, which derive from an internal promoter of CREM gene, was detected in the normal adrenal and in seven of eight adenomas, but in only three of eight carcinomas. Similarly, CREB transcripts were readily detectable in all normal adrenals and adenomas, whereas they were not found in four of eight adrenal carcinomas. To further characterize the carcinomas, telomerase activity and the expression of the ACTH receptor gene were determined. Telomerase activity in the carcinomas resulted in levels significantly higher 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/inducible cAMP early repressor, suggesting that this alteration is not secondary to an upstream disregulation at the receptor level. In conclusion, our results suggest that an alteration in cAMP signaling may be associated with malignancies of the adrenal cortex.

This article has been cited by other articles:

				C Vincent-Dejean, L Cazabat, L Groussin, K Perlemoine, G Fumey, F Tissier, X Bertagna, and J Bertherat Identification of a clinically homogenous subgroup of benign cortisol-secreting adrenocortical tumors characterized by alterations of the protein kinase A (PKA) subunits and high PKA activity. Eur. J. Endocrinol., June 1, 2008; 158(6): 829 - 839. [Abstract] [Full Text] [PDF]

				R. Libe and J. Bertherat Molecular genetics of adrenocortical tumours, from familial to sporadic diseases Eur. J. Endocrinol., October 1, 2005; 153(4): 477 - 487. [Abstract] [Full Text] [PDF]

				C A Longui, S H V Lemos-Marini, B Figueiredo, B B Mendonca, M Castro, R Liberatore Jr, C Watanabe, C L P Lancellotti, M N Rocha, M B Melo, et al. Inhibin {alpha}-subunit (INHA) gene and locus changes in paediatric adrenocortical tumours from TP53 R337H mutation heterozygote carriers J. Med. Genet., May 1, 2004; 41(5): 354 - 359. [Abstract] [Full Text] [PDF]

				P. Luciani, P. Ferruzzi, G. Arnaldi, C. Crescioli, S. Benvenuti, G. Nesi, A. Valeri, I. Greeve, M. Serio, M. Mannelli, et al. Expression of the Novel Adrenocorticotropin-Responsive Gene Selective Alzheimer's Disease Indicator-1 in the Normal Adrenal Cortex and in Adrenocortical Adenomas and Carcinomas J. Clin. Endocrinol. Metab., March 1, 2004; 89(3): 1332 - 1339. [Abstract] [Full Text] [PDF]

				J. Bertherat, L. Groussin, F. Sandrini, L. Matyakhina, T. Bei, S. Stergiopoulos, T. Papageorgiou, I. Bourdeau, L. S. Kirschner, C. Vincent-Dejean, et al. Molecular and Functional Analysis of PRKAR1A and its Locus (17q22-24) in Sporadic Adrenocortical Tumors: 17q Losses, Somatic Mutations, and Protein Kinase A Expression and Activity Cancer Res., September 1, 2003; 63(17): 5308 - 5319. [Abstract] [Full Text] [PDF]

				D. Rosenberg, L. Groussin, E. Jullian, K. Perlemoine, S. Medjane, A. Louvel, X. Bertagna, and J. Bertherat Transcription Factor 3',5'-Cyclic Adenosine 5'-Monophosphate-Responsive Element-Binding Protein (CREB) Is Decreased during Human Adrenal Cortex Tumorigenesis and Fetal Development J. Clin. Endocrinol. Metab., August 1, 2003; 88(8): 3958 - 3965. [Abstract] [Full Text] [PDF]