Nrf2 is commonly activated in papillary thyroid carcinoma, and it controls antioxidant transcriptional responses and viability of cancer cells.

Details

Serval ID
serval:BIB_93C277B91627
Type
Article: article from journal or magazin.
Collection
Publications
Title
Nrf2 is commonly activated in papillary thyroid carcinoma, and it controls antioxidant transcriptional responses and viability of cancer cells.
Journal
Journal of Clinical Endocrinology and Metabolism
Author(s)
Ziros P.G., Manolakou S.D., Habeos I.G., Lilis I., Chartoumpekis D.V., Koika V., Soares P., Kyriazopoulou V.E., Scopa C.D., Papachristou D.J., Sykiotis G.P.
ISSN
1945-7197 (Electronic)
ISSN-L
0021-972X
Publication state
Published
Issued date
2013
Peer-reviewed
Oui
Volume
98
Number
8
Pages
E1422-E1427
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
CONTEXT: The antioxidant transcription factor NFE2-related factor 2 (Nrf2), encoded by NFE2L2, has been implicated as mediator of thyroid cancer cell line resistance to proteasome inhibitors. However, the activity status of the Nrf2 pathway in human thyroid cancer remains unknown.
OBJECTIVE: The aims of this study were assessment of the activity status of the Nrf2 pathway in papillary thyroid carcinoma (PTC) and investigation of its role(s) in antioxidant transcriptional responses and viability of cancer cells.
DESIGN AND SETTING: We conducted retrospective immunohistochemical analyses of PTC specimens, adjacent normal tissue, and benign lesions; assays of viability and gene expression in the PTC cell lines K1 and TPC-1 after genetic/pharmacological manipulation of Nrf2; and DNA sequencing at an academic medical center.
PATIENTS: The study included 42 PTC and 42 benign lesions (24 adenomas and 18 nodular hyperplasias).
MAIN OUTCOME MEASURES: We assessed the abundance of Nrf2, Nqo1, Keap1, and 4HNE; cell line viability and mRNA expression of Nrf2, Nqo1, and Trdx1; and the sequence of NFE2L2, KEAP1, and BRAF.
RESULTS: Nrf2 and its target Nqo1 were undetectable in normal tissue; their levels were significantly higher in PTC than in benign lesions (P < .0001 and P = .024, respectively). The Nrf2 inhibitor Keap1 was variably abundant in PTC, and its levels did not correlate with Nrf2 (P = .37), arguing against decreased levels as the mechanism for Nrf2 activation. The oxidized lipid 4HNE was more abundant in PTC than normal tissue (P < .001), indicating oxidative stress. Nrf2 mediated transcriptional antioxidant responses in both the PTC cell lines K1 and TPC-1 and in the nontransformed cell line TAD2, but it conferred a viability advantage specifically in the PTC cell lines.
CONCLUSIONS: The high activity of Nrf2 in PTC warrants further exploration of this pathway's potential diagnostic, prognostic, and/or therapeutic utility in PTC.
Keywords
Aldehydes/analysis, Antioxidants/metabolism, Carcinoma/metabolism, Carcinoma/pathology, Cell Line, Tumor, Cell Survival, Humans, Intracellular Signaling Peptides and Proteins/genetics, NAD(P)H Dehydrogenase (Quinone)/analysis, NF-E2-Related Factor 2/analysis, NF-E2-Related Factor 2/physiology, Oxidative Stress, Retrospective Studies, Signal Transduction, Thyroid Neoplasms/metabolism, Thyroid Neoplasms/pathology, Transcription, Genetic
Pubmed
Web of science
Open Access
Yes
Create date
20/01/2015 14:37
Last modification date
20/08/2019 15:56
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