Oncogenic Potential of Guanine Nucleotide Stimulatory Factor α Subunit in Thyroid Glands of Transgenic Mice

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 91; no. 22; pp. 10488 - 10492
• Main Authors: Michiels, Francine-Marie, Caillou, Bernard, Talbot, Monique, Dessarps-Freichey, Francoise, Maunoury, Marie-Therese, Schlumberger, Martin, Mercken, Luc, Monier, Roger, Feunteun, Jean
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 25-10-1994; National Acad Sciences
• Subjects: Adenoma; Animals; Autoradiography; Base Sequence; Cattle; Cricetinae; Cricetulus; Crosses, Genetic; Cyclic AMP - metabolism; DNA Primers; Epithelial Cells; Epithelium - metabolism; Follicles; Gene Expression; Genes; Genetic mutation; GTP-Binding Proteins - biosynthesis; Iodine - metabolism; Iodine Radioisotopes; Macromolecular Substances; Mice; Mice, Inbred DBA; Mice, Transgenic; Molecular Sequence Data; Papillae; Point Mutation; Polymerase Chain Reaction; Promoter Regions, Genetic; Thyroglobulin - genetics; Thyroid cancer; Thyroid gland; Thyroid Gland - cytology; Thyroid Gland - metabolism; Thyroxine - blood; Transgenes; Transgenic animals; Triiodothyronine - blood
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.22.10488

Transgenic mice have been used to address the issue of the oncogenic potential of mutant guanine nucleotide stimulatory factor (Gs) α subunit in the thyroid gland. The expression of the mutant Arg-201 → His Gsα 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 Gsα 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.