Expression of cyclic adenosine 3′,5′-monophosphate (cAMP)-responsive element binding protein and inducible-cAMP early repressor genes in growth hormone-secreting pituitary adenomas with or without mutations of the Gsα gene

Alessandro Peri, Barbara Conforti, Silvana Baglioni-Peri, Paola Luciani, Federica Cioppi, Lisa Buci, Sabrina Corbetta, Emilia Ballaré, Mario Serio, Anna Spada

Research output: Contribution to journalArticle

Abstract

In about 30-40% of GH-secreting adenomas, gain-of-function mutations of the Gsα gene, which convert this gene into an oncogene termed gsp, occur. Gsα mutations have been related to pituitary tumorigenesis. We focused on 2 nuclear transcription factors that are final targets of the cAMP-dependent pathway and are positively regulated by cAMP signaling, i.e. the cAMP-responsive element binding protein (CREB) and the inducible cAMP early repressor (ICER), that derives from alternative splicing of cAMP-responsive element modulator gene. We examined 21 GH-secreting adenomas, 8 with (gsp+) and 13 without (gsp-) a mutated Gsα. Analysis of CREB and ICER I/II messenger RNA revealed that the levels of both transcripts were higher in gsp+ than in gsp- tumors (CREB/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mean optical density ± SE, 2.34 ± 0.36 in gsp+ vs. 0.99 ± 0.22 in gsp-, P = 0.003; ICER I/GAPDH, 0.53 ± 0.15 in gsp+ vs. 0.14 ± 0.07 in gsp-, P = 0.01; ICER II/GAPDH, 1.5 ± 0.21 in gsp± vs. 0.83 ± 0.13 in gsp-, P = 0.01), although a few cases in both groups did not display this pattern of expression. Moreover, no positive correlation between the levels of CREB and ICER transcripts was observed, suggesting the possible presence of alterations in the mechanisms by which cAMP signaling directs the expression of CREB and/or ICER genes. Our results indicate a complex pattern of expression of nuclear transcription factors that mediate cAMP action in both gsp+ and gsp- tumors, suggesting that, beside Gsα gene mutations, different and partially unknown molecular events may contribute to the pathogenesis of these tumors.

Original languageEnglish
Pages (from-to)2111-2117
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume86
Issue number5
DOIs
Publication statusPublished - 2001

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

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