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

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...