한빛사 논문
가톨릭대학교
Yoo Ri Kim,1 Ji Eun Oh,1 Min Sung Kim,1 Mi Ran Kang,1 Sang Wook Park,1 Ji Youn Han,2 Hyeon Seok Eom,3 Nam Jin Yoo1 and Sug Hyung Lee1*
1Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea
2Center for Lung Cancer, National Cancer Center of Korea, Goyang, Korea
3Hematology–Oncology Clinic, National Cancer Center of Korea, Goyang, Korea
*Correspondence to:Sug Hyung Lee
Abstract
Nuclear factor erythroid‐related factor 2 (NRF2 ) encodes a transcription factor that induces expression of cytoprotective proteins upon oxidative stress and oncogenic NRF2 mutations have been found in lung and head/neck cancers that inactivate KEAP1‐mediated degradation of NRF2. The aim of this study was to catalogue NRF2 mutations in other human cancers. For this, we analysed 1145 cancer tissues from carcinomas from oesophagus, skin, uterine cervix, lung, larynx, breast, colon, stomach, liver, prostate, urinary bladder, ovary, uterine cervix, and kidney, and meningiomas, multiple myelomas, and acute leukaemias by single‐strand conformation polymorphism (SSCP) assay. We detected NRF2 mutations in oesophagus (8/70; 11.4%), skin (1/17; 6.3%), lung (10/125; 8.0%), and larynx (3/23; 13.0%) cancers. Of note, all of the 22 mutations except one were found in squamous cell carcinomas (SCCs) (95.5%). The mutations were observed within or near DLG and ETGE motifs that are important in NRF2 and KEAP1 interaction. All of the oesophageal SCCs and skin SCCs with the NRF2 mutations showed increased NRF2 expression in the nuclei. However, none of the SCCs from oesophagus and skin harboured KEAP1 mutation. Our study demonstrated here that NRF2 mutation occurs not only in lung and head/neck cancers, but also in oesophageal and skin cancers. Our data suggest that the NRF2 mutation plays a role in the development of SCC and is a feature of SCC.
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