Identification of cyclic adenosine 3',5'-monophosphate response element modulator as an activator of the human sodium/iodide symporter upstream enhancer.

Endocrinology
Mike S FentonJerome M Hershman

Abstract

The lack of Na(+)/I(-) symporter (NIS) gene expression in some thyroid cancer patients has been a major hurdle that limits the efficacy of standard radioactive iodide therapy. The molecular mechanism that contributes to low NIS expression is not well understood. Activated NIS gene expression is stimulated by thyroid-stimulating hormone-mediated cAMP/protein kinase A signaling through a NIS upstream enhancer (NUE). The cAMP pathway is also stimulated by forskolin. In the current work, we studied the mechanism of transcriptional activation of NIS in normal thyroid cells and thyroid cancer cells. We identified the cAMP response element modulator (CREM) activator as a new component of the transcription complex that is important for NIS gene expression. The CREM complex is seen in the normal thyroid cells and BRAF (V600E) thyroid cancer cells (BHP 17-10) but is missing in rearranged in transformation/papillary thyroid carcinoma-1 rearrangement thyroid cancer cells (BHP 2-7). This complex is believed to be responsible for the loss of NUE activity and reduced NIS expression in the BHP 2-7 cell line. In BHP 2-7 cells, forskolin stimulated the thyroid-specific transcription factor Pax 8, but CREM activator mRNA did not increase, and thi...Continue Reading

References

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Citations

Jul 16, 2010·Thyroid : Official Journal of the American Thyroid Association·Mike S FentonJerome M Hershman
Apr 19, 2012·Thyroid : Official Journal of the American Thyroid Association·Nadia PassonGiuseppe Damante
Jul 4, 2012·Pharmacology & Therapeutics·Takahiko Kogai, Gregory A Brent
Jan 18, 2019·Thyroid : Official Journal of the American Thyroid Association·Arístides López-MárquezPilar Santisteban
Apr 2, 2013·Molecular Endocrinology·Robert RingseisKlaus Eder
Oct 1, 2019·Endocrinology and Metabolism·Jierui LiuJun Liang

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