title: The cyclic adenosine 3',5'-monophosphate-responsive factor CREB is constitutively activated in human somatotroph adenomas.
abstract: Oncogenic gsp proteins appear to stimulate the transformation of pituitary somatotrophs by inducing the constitutive activation of adenyl cyclase. Previous work implicating the cAMP-responsive transcription factor CREB as a biochemical intermediate in the proliferative response to cAMP led us to examine whether CREB activity was correspondingly elevated in human somatotroph adenomas. In a series of 15 human GH-secreting tumors, we found that each of these contained elevated levels of Ser133-phosphorylated and, hence, activated CREB compared with nonfunctioning pituitary tumors. Four of the GH-secreting adenomas contained an oncogenic gsp gene by polymerase chain reaction analysis, and two additional adenomas expressed wild-type G alpha s protein at 5- to 10-fold higher levels than nonfunctioning pituitary tumors. As both oncogenic gsp and overexpressed G alpha s proteins can induce Ser133 phosphorylation and cAMP-responsive gene expression in transfected GC somatotroph cells, our studies indicate that these proteins may promote somatotroph transformation in part by inducing the transcription of specific CREB-dependent target genes.
mesh_terms: D000236:Adenoma / Q000378:metabolism*; D000818:Animals; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D010911:Pituitary Neoplasms / Q000378:metabolism*; D051381:Rats; D015533:Transcriptional Activation
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D000242:Cyclic AMP