Overexpression of the Aldo-Keto Reductase Family Protein AKR1B10 Is Highly Correlated with Smokers' Non–Small Cell Lung Carcinomas
Shinichi Fukumoto,Naoko Yamauchi,Hisashi Moriguchi,Yoshitaka Hippo,Akira Watanabe,Junji Shibahara,Hirokazu Taniguchi,Shumpei Ishikawa,Hirotaka Ito,Shogo Yamamoto,Hiroko Iwanari,Mitsugu Hironaka,Yuichi Ishikawa,Toshiro Niki,Yasunori Sohara,Tatsuhiko Kodama,Masaharu Nishimura,Masashi Fukayama,Hirotoshi Dosaka-Akita,Hiroyuki Aburatani +19 more
TLDR
The results suggest that AKR1B10 is a potential diagnostic marker specific to smokers' NSCLCs and might be involved in tobacco-related carcinogenesis.Abstract:
Purpose: Squamous cell carcinoma (SCC) and adenocarcinoma of the lung are currently subject to similar treatment regimens despite distinct differences in histology and epidemiology. The aim of this study is to identify a molecular target with diagnostic and therapeutic values for SCC. Experimental Design: Genes specifically up-regulated in SCC were explored through microarray analysis of 5 SCCs, 5 adenocarcinomas, 10 small cell lung carcinomas, 27 normal tissues, and 40 cancer cell lines. Clinical usefulness of these genes was subsequently examined mainly by immunohistochemical analysis. Results: Seven genes, including aldo-keto reductase family 1, member B10 ( AKR1B10 ), were identified as SCC-specific genes. AKR1B10 was further examined by immunohistochemical analysis of 101 non–small cell lung carcinomas (NSCLC) and its overexpression was observed in 27 of 32 (84.4%) SCCs and 19 of 65 (29.2%) adenocarcinomas. Multiple regression analysis showed that smoking was an independent variable responsible for AKR1B10 overexpression in NSCLCs ( P P Conclusion: AKR1B10 was overexpressed in most cases with SCC, which is closely associated with smoking, and many adenocarcinoma cases of smokers. These results suggest that AKR1B10 is a potential diagnostic marker specific to smokers9 NSCLCs and might be involved in tobacco-related carcinogenesis.read more
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The aldo-keto reductase superfamily and its role in drug metabolism and detoxification.
TL;DR: The aldo-keto reductase (AKR) superfamily comprises enzymes that catalyze redox transformations involved in biosynthesis, intermediary metabolism, and detoxification that play an important role in the phase II detoxification of a large number of pharmaceuticals, drugs, and xenobiotics.
Journal ArticleDOI
Aldo-Keto Reductases and Bioactivation/Detoxication
Yi Jin,Trevor M. Penning +1 more
TL;DR: Aldo-keto reductases are stress-regulated genes and play a central role in the cellular response to osmotic, electrophilic, and oxidative stress.
Journal ArticleDOI
The aldo-keto reductases (AKRs): Overview
TL;DR: The aldo-keto reductase (AKR) protein superfamily contains >190 members that fall into 16 families and are found in all phyla and are now poised to be interrogated using modern genomic and informatics approaches to determine their association with human health and disease.
Journal ArticleDOI
Characterization of the cancer chemopreventive NRF2-dependent gene battery in human keratinocytes: demonstration that the KEAP1-NRF2 pathway, and not the BACH1-NRF2 pathway, controls cytoprotection against electrophiles as well as redox-cycling compounds
A. Kenneth MacLeod,Michael McMahon,Simon Plummer,Larry G. Higgins,Trevor M. Penning,Kazuhiko Igarashi,John D. Hayes +6 more
TL;DR: The KEAP1-NRF2 pathway determines resistance to electrophiles and redox-cycling compounds in human keratinocytes through glutathione-dependent and glutATHione-independent mechanisms and it is shown that AKR1B10,AKR1C1 and AKR 1C2 proteins have potential utility as biomarkers for NRF2 activation in the human.
Journal ArticleDOI
Identification of retinoic acid as an inhibitor of transcription factor Nrf2 through activation of retinoic acid receptor alpha
TL;DR: Cross-talk between Nrf2 and RARα could markedly influence the sensitivity of cells to electrophiles and oxidative stressors and, as a consequence, to carcinogenesis.
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