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B-RafV600E inhibits sodium iodide symporter expression via regulation of DNA methyltransferase 1.

Authors
Choi, YW  | Kim, HJ | Kim, YH | Park, SH | Chwae, YJ  | Lee, J  | Soh, EY  | Kim, JH  | Park, TJ
Citation
Experimental & molecular medicine, 46. : e120-e120, 2014
Journal Title
Experimental & molecular medicine
ISSN
1226-36132092-6413
Abstract
B-RafV600E mutant is found in 40-70% of papillary thyroid carcinoma (PTC) and has an important role in the pathogenesis of PTC. The sodium iodide symporter (NIS) is an integral plasma membrane glycoprotein that mediates active iodide transport into the thyroid follicular cells, and B-RafV600E has been known to be associated with the loss of NIS expression. In this study, we found that B-RafV600E inhibited NIS expression by the upregulation of its promoter methylation, and that specific regions of CpG islands of NIS promoter in B-RafV600E harboring PTC were highly methylated compared with surrounding normal tissue. Although DNA methyltransferase 3a and 3b (DNMT3a,3b) were not increased by B-RafV600E, DNMT1 expression was markedly upregulated in PTC and B-RafV600E expressing thyrocytes. Furthermore, DNMT1 expression was upregulated by B-RafV600E induced NF-κB activation. These results led us to conclude that NIS promoter methylation, which was induced by B-RafV600E, is one of the possible mechanisms involved in NIS downregulation in PTC.
MeSH

DOI
10.1038/emm.2014.68
PMID
25378232
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Hematology-Oncology
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
Journal Papers > School of Medicine / Graduate School of Medicine > Surgery
Journal Papers > School of Medicine / Graduate School of Medicine > Pathology
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
Ajou Authors
김, 장희  |  박, 태준  |  소, 의영  |  이, 정훈  |  최, 용원  |  최, 용준
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