Overexpression of the Aldo-Keto Reductase Family Protein AKR1B10 Is Highly Correlated with Smokers' Non–Small Cell Lung Carcinomas

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 SCCspecific 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 < 0.01) and adenocarcinomas (P < 0.01). AKR1B10 staining was occasionally observed even in squamous metaplasia, a precancerous lesion of SCC.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 smokers' NSCLCs and might be involved in tobacco-related carcinogenesis.

Two subclasses of lung squamous cell carcinoma with different gene expression profiles and prognosis identified by hierarchical clustering and non-negative matrix factorization

“…Aldoketo reductase family 1, member C (AKR1C) is implicated in the conversion of polycyclic aromatic hydrocarbons into active carcinogens in lung (Palackal et al, 2002). Overexpression of AKR1B10 appears characteristic of smokers' non-small-cell lung carcinomas (Fukumoto et al, 2005). The over-represented ectoderm development category consisted mainly of genes involved in epidermal development (e.g.…”

Impact of Smoking Cessation on Global Gene Expression in the Bronchial Epithelium of Chronic Smokers

“…Seven of the eight validated genes overexpressed in current smokers-CYP1B1, four AKRs, ALDH3A1, and NQO1 (Table 2)-are involved in drug and/or carcinogen metabolism (9,10,(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). Polycyclic aromatic hydrocarbons in tobacco smoke are known to bind to and activate the aryl hydrocarbon receptor and thus induce CYP1B1 (10).…”

“…28). AKR1B10 is overexpressed in non-small-cell lung cancer and squamous metaplasia in association with smoking (24,26). AKR1C1, AKR1C2, and AKR1C3 are known to be involved in tobacco carcinogen and/or drug metabolism.…”

Inhibitory effects of polyphenols isolated from Rhus verniciflua on Aldo-keto reductase family 1 B10

“…AKR1B10 is a NADPH-dependent oxidoreductase and reduces various aldehydes and ketones, including endogenous substrates such as retinals, farnesal and geranylgeranial (2,3). AKR1B10 is, however, highly expressed in several types of cancers, including hepatocellular carcinoma (4), lung squamous cell carcinoma, lung adnocarcinoma in smokers (5) and cervical cancer (6). AKR1B10 is also known to be highly active in the reduction of all-trans-and 9-cis-retinaldehyde, with efficiency comparable to retinaldehyde reductase.…”