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Título

PI3K is involved in the IGF-I inhibition of TSH-induced sodium/iodide symporter gene expression

AutorGarcía, Bibian; Santisteban, Pilar
Fecha de publicaciónfeb-2002
EditorEndocrine Society
CitaciónMolecular Endocrinology 16(2): 342-352 (2002)
ResumenHere we studied the role of IGF-I on the regulation of the sodium/iodide symporter (NIS) gene expression in FRTL-5 thyroid cells. IGF-I did not modify NIS mRNA levels but inhibited TSH- and forskolin-induced NIS mRNA expression in a dose-dependent manner. We explored the signaling pathways by which IGF-I mediates the repression of NIS expression. Inhibition of either the MAPK kinase or PKC activities had no effect. Interestingly, inhibition of PI3K blocked IGF-I repression of TSHinduced NIS mRNA and protein levels. This effect takes place at the transcriptional level, as IGF-I inhibited TSH-induced transcription of a luciferase reporter construct containing a 2.8-kb DNA fragment of the rat NIS promoter. The inhibitory effect of IGF-I on the NIS promoter was blocked by the PI3K inhibitor LY294002 and was mimicked by overexpression of a vector harboring the constitutively activated catalytic subunit of PI3K. Using internal deletions of the NIS promoter, we defined a region from -1,947 to -1,152 responsible for the observed IGF-I/PI3K inhibitory effect. When fused to a heterologous promoter, this region inhibits transcription in response to IGF-I. These results demonstrate a central role for PI3K in the repression of NIS gene transcription by IGF-I and suggest the existence, within the above defined promoter region, of putative PI3K-responsive elements.
Descripción11 pages, 6 figures.
Versión del editorhttp://dx.doi.org/10.1210/me.16.2.342
URIhttp://hdl.handle.net/10261/24527
DOI10.1210/me.16.2.342
ISSN0888-8809
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