This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ballaré, E. Articles by Spada, A. Search for Related Content PubMed PubMed Citation Articles by Ballaré, E. Articles by Spada, A.

Activating Mutations of the G_s Gene Are Associated with Low Levels of Gs Protein in Growth Hormone-Secreting Tumors¹

Institute of Endocrine Sciences, Ospedale Maggiore IRCCS, Italian Auxologic Center IRCCS (A.M.D.B.), and the Department of Pharmacology, CNR Center of Cytopharmacology, Scientific Institute San Raffaele, University of Milan (L.V.), Milan, Italy

Address all correspondence and requests for reprints to: Anna Spada, M.D., Istituto di Scienze Endocrine Ospedale Maggiore, IRCCS, Via Francesco Sforza 35, 20122 Milan, Italy. E-mail: endosci{at}imiucca.csi unimi.it.

Evidence suggests the existence of a direct relationship between cellular G_s content and activation of the adenylyl cyclase system. Data on G_s levels in endocrine tumors that depend on cAMP for growth, particularly pituitary adenomas, are still limited. The levels of G_s protein were evaluated in 11 GH-secreting adenomas with G_s mutations (gsp⁺) and 15 without (gsp). Complementary DNAs from gsp⁺ tumors contained very low amounts of wild-type G_s sequences, indicating a preponderance of the mutant G_s transcripts in these tumors. Immunoblotting of G_s protein showed that the two isoforms were present at high levels in all gsp^-, but were undetectable or barely detectable in gsp⁺. The low G_s content in gsp⁺ tumors was not due to a reduction in ribonucleic acid synthesis or stability, as G_s messenger ribonucleic acid levels were similar in wild-type and mutant tissues. Treatment of gsp^- cells with cholera toxin caused a marked reduction of G_s levels. As in other cell systems cholera toxin increases G_s degradation, our data are consistent with an accelerated removal of mutant G_s. This may represent an additional mechanism of feedback response to the constitutive activation of cAMP signaling in pituitary tumors with mutations in the G_s gene.

This article has been cited by other articles:

				S.-Y. Kim, M. Seo, Y. Kim, Y.-I. Lee, J.-M. Oh, E.-A. Cho, J.-S. Kang, and Y.-S. Juhnn Stimulatory Heterotrimeric GTP-binding Protein Inhibits Hydrogen Peroxide-induced Apoptosis by Repressing BAK Induction in SH-SY5Y Human Neuroblastoma Cells J. Biol. Chem., January 18, 2008; 283(3): 1350 - 1361. [Abstract] [Full Text] [PDF]

				D. Romano, K. Magalon, M. Pertuit, R. Rasolonjanahary, A. Barlier, A. Enjalbert, and C. Gerard Conditional Overexpression of the Wild-Type Gs{alpha} as the gsp Oncogene Initiates Chronic Extracellularly Regulated Kinase 1/2 Activation and Hormone Hypersecretion in Pituitary Cell Lines Endocrinology, June 1, 2007; 148(6): 2973 - 2983. [Abstract] [Full Text] [PDF]

				A. Lania, G. Mantovani, and A. Spada Genetics of Pituitary Tumors: Focus on G-Protein Mutations Experimental Biology and Medicine, October 1, 2003; 228(9): 1004 - 1017. [Abstract] [Full Text] [PDF]

				A. Lania, M. Filopanti, S. Corbetta, M. Losa, E. Ballare, P. Beck-Peccoz, and A. Spada Effects of Hypothalamic Neuropeptides on Extracellular Signal-Regulated Kinase (ERK1 and ERK2) Cascade in Human Tumoral Pituitary Cells J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1692 - 1696. [Abstract] [Full Text] [PDF]

				G. Mantovani, E. Ballare, E. Giammona, P. Beck-Peccoz, and A. Spada The Gs{alpha} Gene: Predominant Maternal Origin of Transcription in Human Thyroid Gland and Gonads J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4736 - 4740. [Abstract] [Full Text] [PDF]

				L. S. Weinstein, S. Yu, D. R. Warner, and J. Liu Endocrine Manifestations of Stimulatory G Protein {alpha}-Subunit Mutations and the Role of Genomic Imprinting Endocr. Rev., October 1, 2001; 22(5): 675 - 705. [Abstract] [Full Text] [PDF]

				E. Ballare, L. Persani, A. G. Lania, M. Filopanti, E. Giammona, S. Corbetta, S. Mantovani, M. Arosio, P. Beck-Peccoz, G. Faglia, et al. Mutation of Somatostatin Receptor Type 5 in an Acromegalic Patient Resistant to Somatostatin Analog Treatment J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3809 - 3814. [Abstract] [Full Text] [PDF]

				A. Peri, B. Conforti, S. Baglioni-Peri, P. Luciani, F. Cioppi, L. Buci, S. Corbetta, E. Ballaré, M. Serio, and A. Spada 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 Gs{{alpha}} Gene J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 2111 - 2117. [Abstract] [Full Text]

				G. Mantovani, R. Romoli, G. Weber, V. Brunelli, E. De Menis, S. Beccio, P. Beck-Peccoz, and A. Spada Mutational Analysis of GNAS1 in Patients with Pseudohypoparathyroidism: Identification of Two Novel Mutations J. Clin. Endocrinol. Metab., November 1, 2000; 85(11): 4243 - 4248. [Abstract] [Full Text]

				A. Barlier, I. Pellegrini-Bouiller, G. Gunz, A. J. Zamora, P. Jaquet, and A. Enjalbert Impact of gsp Oncogene on the Expression of Genes Coding for Gs{alpha}, Pit-1, Gi2{alpha}, and Somatostatin Receptor 2 in Human Somatotroph Adenomas: Involvement in Octreotide Sensitivity J. Clin. Endocrinol. Metab., August 1, 1999; 84(8): 2759 - 2765. [Abstract] [Full Text]

				R. Romoli, A. Lania, G. Mantovani, S. Corbetta, L. Persani, and A. Spada Expression of Calcium-Sensing Receptor and Characterization of Intracellular Signaling in Human Pituitary Adenomas J. Clin. Endocrinol. Metab., August 1, 1999; 84(8): 2848 - 2853. [Abstract] [Full Text]