Impact of gsp oncogene on the expression of genes coding for G(s)alpha, Pit-1, G(i)2 alpha, and somatostatin receptor 2 in human somatotroph adenomas: Involvement in octreotide sensitivity

The impact of the gsp oncogene on the expression of genes engaged in the so matotroph cell phenotype remains poorly understood in human somatotroph ade nomas. As the gsp oncogene is associated with an increased octreotide (soma tostatin agonist) sensitivity, a group of 8 somatotroph adenomas bearing th e gsp mutation (gsp+) and another group of 16 adenomas without the mutation (gsp-) were analyzed, all of them presenting variable octreotide sensitivi ties. The expressions of genes encoding for G(s)alpha, Pit-1, G(i2)alpha, a nd SSTR2, involved in the regulation of secretory activity in somatotroph c ells, were assessed by Northern blot. A decreased expression of the G(s)alp ha gene was found in gsp+ tumors, suggesting the existence of a negative fe edback of the oncogenic protein upon its own messenger ribonucleic acid (mR NA). In contrast, G(i2)alpha, Pit-1, and GH messengers were not significant ly different in the groups. A positive correlation between the in vitro and in vivo GH octreotide-induced secretory inhibition and the expression of S STR2 mRNA was found. However, the expression of the gene for SSTR2 appeared not to be different between gsp+ and gsp-, even when the octreotide sensit ivity was significantly higher in the adenomas carrying the mutation. Inter estingly, the SSTR2 gene expression was significantly correlated to those o f G(i2)alpha and Pit-1. In the same way, the G(s)alpha mRNA expression was positively correlated with those of G(i2)alpha and Pit-1. Such correlations strongly suggest a concerted dysregulation of the expression of these gene s in both categories of adenomas. The loss of the octreotide sensitivity re presents one aspect of the dysregulation process that partially results fro m the decreased SSTR2 expression. However, the improvement of the sensitivi ty associated with the presence of the gsp oncogene seems to proceed in a w ay different from SSTR2 expression.