Oncogenic potential of guanine nucleotide stimulatory factor alpha subunit in thyroid glands of transgenic mice.
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.
Michiels
F M
FM
Laboratoire d'Oncologie Moléculaire, Centre National de la Recherche Scientifique Unité de Recherche Associée 1158, Institut Gustave Roussy, Villejuif, France.
Caillou
B
B
Talbot
M
M
Dessarps-Freichey
F
F
Maunoury
M T
MT
Schlumberger
M
M
Mercken
L
L
Monier
R
R
Feunteun
J
J
D000818:Animals; D001345:Autoradiography; D001483:Base Sequence; D002417:Cattle; D006224:Cricetinae; D003412:Cricetulus; D003433:Crosses, Genetic; D000242:Cyclic AMP / Q000378:metabolism; D017931:DNA Primers; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000096:biosynthesis*; D015870:Gene Expression; D007455:Iodine / Q000378:metabolism; D007457:Iodine Radioisotopes; D046911:Macromolecular Substances; D051379:Mice; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D013954:Thyroglobulin / Q000235:genetics; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism*; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D017931:DNA Primers; D007457:Iodine Radioisotopes; D046911:Macromolecular Substances; D014284:Triiodothyronine; D013954:Thyroglobulin; D007455:Iodine; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D013974:Thyroxine