Activating mutations of the G(s)α gene are associated with low levels of Gsα protein in growth hormone-secreting tumors

Emilia Ballaré, Simona Mantovani, Andrea Lania, Anna M. Di Blasio, Lucia Vallar, Anna Spada

Research output: Contribution to journalArticle

Abstract

Evidence suggests the existence of a direct relationship between cellular G(s)α content and activation of the adenylyl cyclase system. Data on G(s)α levels in endocrine tumors that depend on cAMP for growth, particularly pituitary adenomas, are still limited. The levels of G(s)α protein were evaluated in 11 GH-secreting adenomas with G(s)α mutations (gsp+) and 15 without (gsp). Complementary DNAs from gsp+ tumors contained very low amounts of wild-type G(s)α sequences, indicating a preponderance of the mutant G(s)α transcripts in these tumors. Immunoblotting of G(s)α 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)α content in gsp+ tumors was not due to a reduction in ribonucleic acid synthesis or stability, as G(s)α 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)α levels. As in other cell systems cholera toxin in creases G(s)α degradation, our data are consistent with an accelerated removal of mutant G(s)α. 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)α gene.

Original languageEnglish
Pages (from-to)4386-4390
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Volume83
Issue number12
Publication statusPublished - 1998

Fingerprint

Growth Hormone
Tumors
Genes
Mutation
Cholera Toxin
Pituitary Neoplasms
Neoplasms
Proteins
RNA
Chemical activation
Immunoblotting
Adenylyl Cyclases
Adenoma
Protein Isoforms
Complementary DNA
Cells
Tissue
Feedback
Growth
Degradation

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

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Activating mutations of the G(s)α gene are associated with low levels of Gsα protein in growth hormone-secreting tumors. / Ballaré, Emilia; Mantovani, Simona; Lania, Andrea; Di Blasio, Anna M.; Vallar, Lucia; Spada, Anna.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 83, No. 12, 1998, p. 4386-4390.

Research output: Contribution to journalArticle

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