title: Impact of gsp oncogene on the expression of genes coding for Gsalpha, Pit-1, Gi2alpha, and somatostatin receptor 2 in human somatotroph adenomas: involvement in octreotide sensitivity.
abstract: The impact of the gsp oncogene on the expression of genes engaged in the somatotroph cell phenotype remains poorly understood in human somatotroph adenomas. As the gsp oncogene is associated with an increased octreotide (somatostatin agonist) sensitivity, a group of 8 somatotroph adenomas bearing the gsp mutation (gsp+) and another group of 16 adenomas without the mutation (gsp-) were analyzed, all of them presenting variable octreotide sensitivities. The expressions of genes encoding for G(s)alpha, Pit-1, G(i2)alpha, and SSTR2, involved in the regulation of secretory activity in somatotroph cells, were assessed by Northern blot. A decreased expression of the G(s)alpha gene was found in gsp + tumors, suggesting the existence of a negative feedback of the oncogenic protein upon its own messenger ribonucleic acid (mRNA). In contrast, G(i2)alpha, Pit-1, and GH messengers were not significantly different in the groups. A positive correlation between the in vitro and in vivo GH octreotide-induced secretory inhibition and the expression of SSTR2 mRNA was found. However, the expression of the gene for SSTR2 appeared not to be different between gsp + and gsp-, even when the octreotide sensitivity was significantly higher in the adenomas carrying the mutation. Interestingly, the SSTR2 gene expression was significantly correlated to those of G(i2)alpha and Pit-1. In the same way, the G(s)alpha mRNA expression was positively correlated with those of Gi2alpha and Pit-1. Such correlations strongly suggest a concerted dysregulation of the expression of these genes in both categories of adenomas. The loss of the octreotide sensitivity represents one aspect of the dysregulation process that partially results from the decreased SSTR2 expression. However, the improvement of the sensitivity associated with the presence of the gsp oncogene seems to proceed in a way different from SSTR2 expression.
authors.affiliation: UMR 6544, Centre National de la Recherche Scientifique, Université de la Méditerranée, Institut Jean Roche, Faculté de Médecine Nord, Marseille, France. barlier.a@jean-roche.univ-mrs.fr
authors.forename: A
authors.initials: A
authors.lastname: Barlier
authors.forename: I
authors.initials: I
authors.lastname: Pellegrini-Bouiller
authors.forename: G
authors.initials: G
authors.lastname: Gunz
authors.forename: A J
authors.initials: AJ
authors.lastname: Zamora
authors.forename: P
authors.initials: P
authors.lastname: Jaquet
authors.forename: A
authors.initials: A
authors.lastname: Enjalbert
mesh_terms: D000236:Adenoma / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D019382:Human Growth Hormone / Q000235:genetics; D006801:Humans; D009154:Mutation; D015282:Octreotide / Q000494:pharmacology*; D009857:Oncogenes; D010911:Pituitary Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis*; D017481:Receptors, Somatostatin / Q000235:genetics*; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C494187:POU1F1 protein, human; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D019382:Human Growth Hormone; C093733:somatostatin receptor 2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019205:GTP-Binding Protein alpha Subunits, Gs; D015282:Octreotide