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B-RafV600E inhibits sodium iodide symporter expression via regulation of DNA methyltransferase 1.
MedLine Citation:
PMID:  25378232     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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.
Authors:
Yong Won Choi; Hyun-Ju Kim; Young Hwa Kim; So Hyun Park; Yong Jun Chwae; Jeonghun Lee; Euy Young Soh; Jang-Hee Kim; Tae Jun Park
Publication Detail:
Type:  Journal Article     Date:  2014-11-07
Journal Detail:
Title:  Experimental & molecular medicine     Volume:  46     ISSN:  2092-6413     ISO Abbreviation:  Exp. Mol. Med.     Publication Date:  2014  
Date Detail:
Created Date:  2014-11-07     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9607880     Medline TA:  Exp Mol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e120     Citation Subset:  IM    
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