AKR1B10: A New Diagnostic Marker of Non–Small Cell Lung Carcinoma in Smokers

Penning, T.M.

doi:10.1158/1078-0432.ccr-05-0071

Cited by 90 publications

(75 citation statements)

References 21 publications

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“…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).…”

Section: Discussionmentioning

confidence: 99%

“…AKR1C1, AKR1C2, and AKR1C3 are known to be involved in tobacco carcinogen and/or drug metabolism. AKR1C1 overexpression is correlated with a poor prognosis of nonsmall-cell lung cancer and is associated with chemotherapeutic drug resistance (25,29). Data suggest that a potential role of AKR1B10 in retinoic acid signaling (30) may be a factor in the negative effects of retinoic acid (retinoids) and its relative β-carotene in smokers in chemoprevention trials (3)(4)(5)(6)(7).…”

Section: Discussionmentioning

confidence: 99%

“…Data suggest that a potential role of AKR1B10 in retinoic acid signaling (30) may be a factor in the negative effects of retinoic acid (retinoids) and its relative β-carotene in smokers in chemoprevention trials (3)(4)(5)(6)(7). Several studies have shown that overexpression of AKR1C1, AKR1C2, or AKR1C3 contributes to the resistance of various tumor types, including lung cancer, to cisplatin-based chemotherapy (25,(31)(32)(33).…”

Section: Discussionmentioning

confidence: 99%

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

Zhang

Lee

Tang

et al. 2008

Cancer Prevention Research

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Cigarette smoke is the major cause of lung cancer and can interact in complex ways with drugs for lung cancer prevention or therapy. Molecular genetic research promises to elucidate the biological mechanisms underlying divergent drug effects in smokers versus nonsmokers and to help in developing new approaches for controlling lung cancer. The present study compared global gene expression profiles (determined via Affymetrix microarray measurements in bronchial epithelial cells) between chronic smokers, former smokers, and never smokers. Smoking effects on global gene expression were determined from a combined analysis of three independent data sets. Differential expression between current and never smokers occurred in 591 of 13,902 measured genes (P < 0.01 and >2-fold change; pooled data)-a profound effect. In contrast, differential expression between current and former smokers occurred in only 145 of the measured genes (P < 0.01 and >2-fold change; pooled data). Nine of these 145 genes showed consistent and significant changes in each of the three data sets (P < 0.01 and >2-fold change), with eight being down-regulated in former smokers. Seven of the eight down-regulated genes, including CYP1B1 and three AKR genes, influence the metabolism of carcinogens and/or therapeutic/chemopreventive agents. Our data comparing former and current smokers allowed us to pinpoint the genes involved in smoking-drug interactions in lung cancer prevention and therapy. These findings have important implications for developing new targeted and dosing approaches for prevention and therapy in the lung and other sites, highlighting the importance of monitoring smoking status in patients receiving oncologic drug interventions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Zhang

Lee

Tang

et al. 2008

Cancer Prevention Research

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“…AKR1B10 is also known to be highly active in the reduction of all-trans-and 9-cis-retinaldehyde, with efficiency comparable to retinaldehyde reductase. Thus, an increase in AKR1B10 activity seriously inhibits retinoic acid synthesis, which can be associated with subsequent loss of cell differentiation and cancer development (7). Recent work showed that down-regulation of the AKR1B10 gene using siRNA promoted cell death in colorectal cancer cells through enhanced cytotoxicity of reactive carbonyls produced from lipid peroxidation (8).…”

Section: Introductionmentioning

confidence: 99%

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

Song¹,

Lee²,

Lee³

et al. 2010

BMB Reports

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Aldo-keto reductase family 1 B10 (AKR1B10) is a member of the NADPH-dependent aldo-keto reductase (AKR) superfamily, and has been considered to be a potential cancer therapeutic target. Total extract from the bark of Rhus verniciflua (Toxicodendron vernicifluum (Stokes)) showed AKR1B10 inhibitory activity. To identify the active compounds from R. verniciflua responsible for AKR1B10 inhibition, nine compounds were isolated via bioactivity-guided isolation and tested for their effects against recombinant human AKR1B10 (rhAKR1B10). Results showed that butein, isolated from the ethyl acetate fraction, was most able to inhibit rhAKR1B10. The inhibitory rate of butein against rhAKR1B10 was 42.86% at 1 μM with an IC50 value of 1.47 μM, and enzyme kinetic analysis revealed its inhibition mode to be uncompetitive. [BMB reports 2010; 43(4): 268-272]

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“…AKR1B10 is primarily expressed in the colon and small intestine with low levels in the liver, thymus, prostate, and testis (1). However, this gene is overexpressed in 54% of human hepatocellular carcinoma, 84.4% of lung squamous cell carcinoma, and 29.2% of lung adenocarcinoma in smokers, making it a potential diagnostic and/or prognostic marker (1,6,7). AKR1B10 is an enzyme that efficiently catalyzes the reduction of carbonyls to corresponding alcohols with NADPH as a co-enzyme (1).…”

mentioning

confidence: 99%

Aldo-keto Reductase Family 1 B10 Affects Fatty Acid Synthesis by Regulating the Stability of Acetyl-CoA Carboxylase-α in Breast Cancer Cells

Yan

et al. 2008

Journal of Biological Chemistry

140

122

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Recent studies have demonstrated that aldo-keto reductase family 1 B10 (AKR1B10), a novel protein overexpressed in human hepatocellular carcinoma and non-small cell lung carcinoma, may facilitate cancer cell growth by detoxifying intracellular reactive carbonyls. This study presents a novel function of AKR1B10 in tumorigenic mammary epithelial cells (RAO-3), regulating fatty acid synthesis. In RAO-3 cells, Sephacryl-S 300 gel filtration and DEAE-Sepharose ion exchange chromatography demonstrated that AKR1B10 exists in two distinct forms, monomers (ϳ40 kDa) bound to DEAE-Sepharose column and protein complexes (ϳ300 kDa) remaining in flow-through. Co-immunoprecipitation with AKR1B10 antibody and protein mass spectrometry analysis identified that AKR1B10 associates with acetyl-CoA carboxylase-␣ (ACCA), a rate-limiting enzyme of de novo fatty acid synthesis. This association between AKR1B10 and ACCA proteins was further confirmed by co-immunoprecipitation with ACCA antibody and pulldown assays with recombinant AKR1B10 protein. Intracellular fluorescent studies showed that AKR1B10 and ACCA proteins colocalize in the cytoplasm of RAO-3 cells. More interestingly, small interfering RNA-mediated AKR1B10 knock down increased ACCA degradation through ubiquitination-proteasome pathway and resulted in >50% decrease of fatty acid synthesis in RAO-3 cells. These data suggest that AKR1B10 is a novel regulator of the biosynthesis of fatty acid, an essential component of the cell membrane, in breast cancer cells.Aldo-keto reductase family 1 B10 (AKR1B10, 2 also designated aldose reductase-like-1, ARL-1) is a novel protein identified from human hepatocellular carcinoma (1). This protein belongs to the aldo-keto reductase superfamily, a group of proteins implicated in intracellular detoxification, cell carcinogenesis, and cancer therapeutics (2-5). AKR1B10 is primarily expressed in the colon and small intestine with low levels in the liver, thymus, prostate, and testis (1). However, this gene is overexpressed in 54% of human hepatocellular carcinoma, 84.4% of lung squamous cell carcinoma, and 29.2% of lung adenocarcinoma in smokers, making it a potential diagnostic and/or prognostic marker (1, 6, 7). AKR1B10 is an enzyme that efficiently catalyzes the reduction of carbonyls to corresponding alcohols with NADPH as a co-enzyme (1). Recent studies demonstrate that AKR1B10 expression facilitates growth of cancer cells, enhances their clonogenic capability, and reduces their susceptibility to reactive carbonyls such as acrolein and crotonaldehyde (8, 9). In vitro, AKR1B10 also shows strong enzymatic activity toward all-trans-retinal, 9-cis-retinal, and 13-cis-retinal, reducing them to the corresponding retinols. The diversity of retinal metabolism may diminish intracellular retinoic acid, a signaling molecule regulating cell proliferation and differentiation (4, 10).The current study presents a novel biological function of AKR1B10, regulating long chain fatty acid synthesis, in human breast cancer cells. During tumorigenic transformatio...

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AKR1B10: A New Diagnostic Marker of Non–Small Cell Lung Carcinoma in Smokers

Cited by 90 publications

References 21 publications

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

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

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

Aldo-keto Reductase Family 1 B10 Affects Fatty Acid Synthesis by Regulating the Stability of Acetyl-CoA Carboxylase-α in Breast Cancer Cells

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