title: Gene expression profile in thyroid of transgenic mice overexpressing the adenosine receptor 2a.
abstract: Mutations of the TSH receptor leading to constitutive activation of the cAMP cascade are responsible for the development of hot nodules, if arising in a somatic cell, and nonautoimmune hyperthyroidism, when occurring in a germinal cell. An animal model of constitutive activation of the thyroid cAMP cascade has been obtained by generating transgenic mice expressing the adenosine receptor (Tg-A2aR) under the control of the thyroglobulin promoter. These mice develop huge goiters and die prematurely due to hyperthyroidism induced cardiac failure. To identify new genes involved in the tumorigenic pathway of the thyroid, we designed a protocol using microarray technology to study the differential expression, between normal and transgenic thyroid, of +/-13,000 genes. A total of 360 genes or expressed sequence tags showed a strong modulation with background corrected values of fluorescence superior to 2-fold change. The modulated genes were classified according to their proposed gene ontology functions. Approximately half of them were up-regulated. The function of the majority of these genes in thyroid physiology is still to be determined. Some of them, like IGF-I or IGF binding protein 3 or 5, may play an important role in the development of thyroid nodules through paracrine mechanisms. This study demonstrates the feasibility of sequentially following the cascade of events leading to the formation of benign tumors such as hot thyroid nodule or hyperfunctional goiter.
authors.affiliation: Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Faculté de Médecine de l'Université Libre de Bruxelles, Belgium. jcgoffar@ulb.ac.be.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Goffard
authors.forename: Ling
authors.initials: L
authors.lastname: Jin
authors.forename: Hortensia
authors.initials: H
authors.lastname: Mircescu
authors.forename: Paul
authors.initials: P
authors.lastname: Van Hummelen
authors.forename: Catherine
authors.initials: C
authors.lastname: Ledent
authors.forename: Jacques-Emile
authors.initials: JE
authors.lastname: Dumont
authors.forename: Bernard
authors.initials: B
authors.lastname: Corvilain
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction / Q000379:methods; D011401:Promoter Regions, Genetic; D043705:Receptor, Adenosine A2A / Q000235:genetics* / Q000502:physiology; D013954:Thyroglobulin / Q000235:genetics; D013961:Thyroid Gland / Q000502:physiology*
chemical_list: D043705:Receptor, Adenosine A2A; D013954:Thyroglobulin