G(s)alpha-identification of a gene highly expressed by insulinoma and other endocrine tumors

Background. The isolation of mRNA molecules that are either uniquely or more highly expressed by tumor and not normal tissue is a powerful tool in the study of cell regulation and growth. To this end we constructed a complementary DNA (cDNA) library from messenger RNA (mRNA) isolated from a human insulinoma and, by differential hybridization with cDNA from both normal pancreas and insulinoma, isolated clones more highly expressed by insulinoma. Methods. Total RNA was isolated from human insulinoma and normal pancreas and purified to mRNA by oligo (dT) column. An insulinoma cDNA library was constructed and screened with ³²P-labeled cDNA from pancreas and insulinoma. Northern blots from insulinoma, pancreas, carcinomas, normal endocrine tissues, and endocrine tumors were then probed with the ³²P- labeled inserts. Results. Two clones that consistently hybridized with ³²P cDNA from insulinoma and not pancreas proved to represent mRNAs for insulin and the α subunit of the G(s) protein. There was a markedly higher expression (30-fold) of the gene for G(s)α in mRNA from insulinoma compared with normal pancreas by Northern blot analysis. We found G(s)α to be more highly expressed by a pheochromocytoma, a corticotropin-producing islet cell tumor of the pancreas, and a corticotropin-producing thymic carcinoid (up to 35-fold) compared with normal pancreas, whereas normal endocrine tissues, a parathyroid adenoma, thyroid follicular adenoma, gastrinoma, and several carcinomas showed no expression. Conclusions. This study showed that G(s)α is highly expressed in insulinoma and certain endocrine tumors. It is not expressed in several cancers or normal endocrine tissues. Others have implicated mutated G(s) proteins in the tumorigenesis of pituitary and thyroid tumors. G proteins are also known to mediate hormonal transmembrane signaling. Its overexpression in four of seven endocrine tumors tested suggests that it may have a role in the unregulated hormone secretion and/or a role in the tumorigenesis of differentiated endocrine tumors.