Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thyrotropin stimulates the growth and proliferation of thyroid cells in vivo. Starting in the 1970, we have progressively shown that these effects could be reproduced in vitro in dog thyroid cells in primary culture. They are accompanied by the expression of differentiation. All the effects of thyrotropin are mediated by the cyclic AMP cascade. The best argument that this concept applies in vivo is the generation of hyperfunctioning adenoma involving the whole gland in transgenic mice expressing the constitutively active adenosine A2 receptor in the thyroid.
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PMID:The TSH cyclic AMP cascade in the control of thyroid cell proliferation: the story of a concept. 172 32

Mouse transgenic models that develop thyroid diseases were generated. All transgenes were driven by the thyroid specific promoter of the thyroglobulin gene. The tissue specificity of the promoter was investigated by using the bacterial chloramphenicol acetyl transferase gene as reporter. The expression of an adenosine A2a receptor resulted in the permanent activation of the cAMP cascade. As a consequence, the transgenic mice developed severe hyperthyroidism and a large goiter, demonstrating in vivo the role of the cAMP cascade in the promotion of both function and proliferation of the thyroid cell. These mice constitute a model for autonomous hyperfunctional adenoma and non-autoimmune familial hyperthyroidism, where mutant thyrotropin receptors stimulate the cAMP cascade constitutively. In another transgenic model, the function of the retinoblastoma susceptibility gene product RB1 (and of related proteins) was inhibited by expression of the E7 oncoprotein of human papillomavirus type 16. The result was the development of a differentiated and normofunctional colloid goiter, with the progressive development of differentiated malignant lesions. This model suggests the essential role of RB1 and related proteins in the negative control of proliferation that characterizes thyroid cells in the adult. Other transgenic models of thyroid diseases are discussed.
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PMID:Transgenic models for proliferative and hyperfunctional thyroid diseases. 898 22

Mouse transgenic models that develop thyroid diseases were generated. All transgenes were driven by the thyroid specific promoter of the thyroglobulin gene. The tissue specificity of the promoter was investigated by using the bacterial chloramphenicol acetyltransferase gene as reporter. The expression of the adenosine A2a receptor resulted in the permanent activation of the cAMP cascade. As a consequence, transgenic mice developed severe hyperthyroidism and a large goiter, demonstrating in vivo the role of the cAMP cascade in the promotion of both function and proliferation of the thyroid cell. These mice constitute a model for autonomous hyperfunctional adenoma and non autoimmune familial hyperthyroidism, where mutant of thyrotropin receptors stimulate the cAMP cascade constitutively. The expression of a mutant of the alpha 1B adrenergic receptor resulted in the constitutive activation of both the cAMP and IP3-CA++ cascades, growth stimulation, hyperfunction, cell degeneracy attributed to the overproduction of free radicals, and development of malignancies. The expression of the SV40 large T antigen promoted the development of aggressive undifferentiated tumors mimicking the phenotype of human anaplastic carcinomas and embryonal tumors. In another transgenic model, the function of the retinoblastoma susceptibility gene product RB1 (and of related proteins) was inhibited by expressing the E7 oncoprotein of human papillomavirus type 16. The result was the development of a differentiated and normofunctional colloid goiter, with progressive development of differentiated malignant lesions. This model suggests the essential role of RB1 and related proteins in the negative control of proliferation that characterizes thyroid cells in the adult. Other transgenic models of thyroid diseases are discussed.
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PMID:[Transgenic mouse models. Their interest in thyroid tumors]. 975 58