MAPK and SHH pathways modulate type 3 deiodinase expression in papillary thyroid carcinoma

Endocrine-related Cancer
Mírian RomittiAna Luiza Maia

Abstract

Type 3 deiodinase (DIO3, D3) is reactivated in human neoplasias. Increased D3 levels in papillary thyroid carcinoma (PTC) have been associated with tumor size and metastatic disease. The objective of this study is to investigate the signaling pathways involved in DIO3 upregulation in PTC. Experiments were performed in human PTC cell lines (K1 and TPC-1 cells) or tumor samples. DIO3 mRNA and activity were evaluated by real-time PCR and ion-exchange column chromatography respectively. Western blot analysis was used to determine the levels of D3 protein. DIO3 gene silencing was performed via siRNA transfection. DIO3 mRNA levels and activity were readily detected in K1 (BRAF(V6) (0) (0E)) and, at lower levels, in TPC-1 (RET/PTC1) cells (P<0.007 and P=0.02 respectively). Similarly, DIO3 mRNA levels were higher in PTC samples harboring the BRAF(V600E) mutation as compared with those with RET/PTC1 rearrangement or negative for these mutations (P<0.001). Specific inhibition of BRAF oncogene (PLX4032, 3 μM), MEK (U0126, 10-20 μM) or p38 (SB203580, 10-20 μM) signaling was associated with decreases in DIO3 expression in K1 and TPC-1 cells. Additionally, the blockage of the sonic hedgehog (SHH) pathway by cyclopamine (10  μM) resulted in m...Continue Reading

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Citations

Sep 13, 2016·The Tohoku Journal of Experimental Medicine·Branislav R RovcaninIvan R Paunovic
Oct 19, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Huy Gia VuongTetsuo Kondo
Sep 21, 2017·Endocrine-related Cancer·Iuri Martin GoemannAna Luiza Maia
Nov 8, 2018·Endocrine-related Cancer·Iuri Martin GoemannAna Luiza Maia
Apr 30, 2019·Endocrine Reviews·Antonio C BiancoBarbara M L C Bocco
Dec 10, 2016·Endocrine-related Cancer·Deborah J Marsh, Charis Eng
Nov 7, 2019·Frontiers in Endocrinology·Carla Fernanda NavaAna Luiza Maia
Jun 3, 2021·Genes·Lilla KrokkerHenriett Butz

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