Oncogenic potential of guanine nucleotide stimulatory factor alpha subunit in thyroid glands of transgenic mice.
- 25 October 1994
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 91 (22) , 10488-10492
- https://doi.org/10.1073/pnas.91.22.10488
Abstract
Transgenic mice have been used to address the issue of the oncogenic potential of mutant guanine nucleotide stimulatory factor (Gs) alpha subunit in the thyroid gland. The expression of the mutant Arg-201-->His Gs alpha subunit transgene has been directed to murine thyroid epithelial cells by bovine thyroglobulin promoter. The transgenic animals develop hyperfunctioning thyroid adenomas with increased intracellular cAMP levels and high uptake of [125I]iodine and produced elevated levels of circulating triiodothyronine and thyroxine. These animals demonstrate that the mutant form of Gs alpha subunit carries an oncogenic activity, thus supporting the model that deregulation of cAMP level alters growth control in thyroid epithelium. These animals represent models for humans with autonomously functioning thyroid nodules.Keywords
This publication has 27 references indexed in Scilit:
- Germline mutations in the thyrotropin receptor gene cause non–autoimmune autosomal dominant hyperthyroidismNature Genetics, 1994
- Suppression of Ras-Induced Transformation of NIH 3T3 Cells by Activated Gα SScience, 1994
- Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomasNature, 1993
- Structural elements of Gα subunits that interact with Gβγ, receptors, and effectorsCell, 1993
- Transgenic Models of Tumor DevelopmentScience, 1991
- Oncogenes and anti‐oncogenes; the molecular basis of tumour behaviourThe Journal of Pathology, 1991
- The GTPase superfamily: conserved structure and molecular mechanismNature, 1991
- Activating point mutations of the gsp oncogene in human thyroid adenomasMolecular Carcinogenesis, 1991
- GTPase inhibiting mutations activate the α chain of Gs and stimulate adenylyl cyclase in human pituitary tumoursNature, 1989
- The cyclic AMP-mediated stimulation of cell proliferationTrends in Biochemical Sciences, 1989