Costimulation of adenylyl cyclase and phospholipase C by a mutant alpha 1B-adrenergic receptor transgene promotes malignant transformation of thyroid follicular cells.

Détails

ID Serval
serval:BIB_10CD25FB7882
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Costimulation of adenylyl cyclase and phospholipase C by a mutant alpha 1B-adrenergic receptor transgene promotes malignant transformation of thyroid follicular cells.
Périodique
Endocrinology
Auteur(s)
Ledent C., Denef J.F., Cottecchia S., Lefkowitz R., Dumont J., Vassart G., Parmentier M.
ISSN
0013-7227 (Print)
ISSN-L
0013-7227
Statut éditorial
Publié
Date de publication
1997
Volume
138
Numéro
1
Pages
369-378
Langue
anglais
Résumé
Proliferation of thyroid follicular cells is controlled by three intra-cellular cascades [cAMP, inositol 1,4,5-triphosphate (IP3)/Ca2+/diacylglycerol (DAG), and tyrosine kinases] that are activated by distinct extracellular signals and receptors. We had previously generated a transgenic mouse model in which the cAMP cascade was permanently stimulated in thyroid cells by an adenosine A2a receptor (Tg-A2aR model). In the present work, we have generated a transgenic model characterized by the chronic stimulation of both adenylyl cyclase and phospholipase C in thyroid follicular cells. The bovine thyroglobulin gene promoter was used to direct the expression of a constitutively active mutant of the alpha 1B adrenergic receptor, which is known to couple to both cascades in transfected cell lines. The expression of the transgene resulted, as expected, in the activation of phospholipase C and adenylyl cyclase, as demonstrated by the direct measurement of IP3 and cAMP in thyroid tissue. The phenotype resulting from this dual stimulation included growth stimulation, hyperfunction, cell degeneracy attributed to the overproduction of free radicals, and the development of malignant nodules invading the capsule, muscles, and blood vessels. Differentiated metastases were found occasionally in old animals. The development of malignant lesions was more frequent and of earlier onset than in our previous Tg-A2aR model, in which only the cAMP cascade was stimulated. These observations demonstrate that the cAMP and IP3/Ca2+/DAG cascades can cooperate in vivo toward the development of thyroid follicular cell malignancies.
Mots-clé
Adenylate Cyclase/metabolism, Animals, Cattle, Cell Transformation, Neoplastic, Enzyme Activation, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Transgenic, Mutation, Phenotype, Receptors, Adrenergic, alpha-1/genetics, Receptors, Adrenergic, alpha-1/physiology, Thyroid Gland/pathology, Transgenes, Type C Phospholipases/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 11:06
Dernière modification de la notice
20/08/2019 12:38
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