Identification and expression analysis of the aldo–ketoreductase1-B10 gene in primary malignant liver tumours

Heringlake, Stefan; Hofdmann, Michael; Fiebeler, Anette; Manns, Michael P.; Schmiegel, Wolff; Tannapfel, Andrea

doi:10.1016/j.jhep.2009.11.005

Cited by 87 publications

(93 citation statements)

References 51 publications

(54 reference statements)

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“…Other studies found that HCCs with low AKR1B10 levels were highly proliferative, poorly differentiated and had a poor prognosis (23,24). In agreement with these studies, the present study identified that AKR1B10 mRNA levels were elevated in HCCs, and that prognosis (RFS and OS) was worse in cases in which the amounts of AKR1B10 mRNA were lower in HCC tissue than in CN tissue.…”

Section: Discussionsupporting

confidence: 91%

“…As shown by Zhang et al (22), AKR1B10 promotes pancreatic carcinogenesis via modulation of the K-RAS/E-cadherin pathway. Several studies demonstrated AKR1B10 expression in HCC via immunohistochemistry (23)(24)(25)(26). To the best of our knowledge, however, there are no reports comparing AKR1B10 expression in HCC and CN tissue or determining its association with HCC prognosis.…”

Section: Discussionmentioning

confidence: 99%

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Prognostic significance of AKR1B10 gene expression in hepatocellular carcinoma and surrounding non-tumorous liver tissue

et al. 2016

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Abstract. When assessing outcome in hepatocellular carcinoma (HCC), it is important to consider prognostic factors in background non-tumorous liver tissue as well as in the tumor, since multiple occurrence is associated with background liver status such as hepatitis. The current study aimed to elucidate molecular prognostic predictors that have an association with HCC background non-tumorous tissue. Microarray expression profiling identified aldo-keto reductase family 1, member B10 (AKR1B10) as a putative non-tumorous prognostic factor, and AKR1B10 gene expression was investigated in 158 curatively resected HCC cases by reverse transcription-quantitative polymerase chain reaction. AKR1B10 expression (AKR1B10 value/GAPDH value x 1,000) was significantly higher in tumor tissue (median, 9.2200; range, 0.0003-611.0200; n=158) than in the corresponding non-tumorous tissue (median, 0.5461; range, 0.0018-69.0300; n=158) (P<0.001). When the samples were grouped according to AKR1B10 expression in tumor tissue relative to non-tumorous tissue, tumor

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Prognostic significance of AKR1B10 gene expression in hepatocellular carcinoma and surrounding non-tumorous liver tissue

et al. 2016

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“…These reports collectively emphasize that AKR1 isozymes such as AKR1B10 and AKR1B8 may play a vital role in modulating the development of ulcerative colitis and colitis-associated colorectal cancer in mammals. However, the mechanisms underlying AKR1B10 overexpression in many non-digestive tract cancers [12,13,15,18] are still not well elucidated, therefore efforts are needed to discover the relationship between AKR1B10 overexpression and cancer formation.…”

Section: Akr1b10 In Cancer Formationmentioning

confidence: 99%

“…However, it presents an opposite expression rule in cancer tissues. AKR1B10 is overexpressed in many non-digestive tract solid cancers such as hepatocellular carcinoma [2], various types of lung cancer including lung squamous cell carcinomas [12] and smoking related lung adenocarcinomas [13], cholangiocarcinomas [12], pancreatic carcinomas [14], and breast carcinomas [15]. On the contrary, the expression of AKR1B10 is downregulated in gastrointestinal cancer [16,17].…”

Section: Introductionmentioning

confidence: 99%

Aldo-Keto Reductase Family 1 Member B10 Inhibitors: Potential Drugs for Cancer Treatment

Li¹,

He²,

Luo³

et al. 2016

PRA

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Cytosolic NADPH-dependent reductase AKR1B10 is a member of the aldo-keto reductase (AKR) superfamily. This enzyme is normally expressed in the gastrointestinal tract. However, it is overexpressed in many solid tumors, such as hepatocarcinoma, lung cancer and breast cancer. AKR1B10 may play a role in the formation and development of carcinomas through multiple mechanisms including detoxification of cytotoxic carbonyls, modulation of retinoic acid level, and regulation of cellular fatty acid synthesis and lipid metabolism. Studies have suggested that AKR1B10 may be a useful biomarker for cancer diagnosis and a potential target for cancer treatment. Over the last decade, a number of AKR1B10 inhibitors including aldose reductase inhibitors (ARIs), endogenous substances, natural-based derivatives and synthetic compounds have been developed, which could be novel anticancer drugs. This review provides an overview on related articles and patents about AKR1B10 inhibitors, with a focus on their inhibition selectivity and mechanism of function.

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“…1) Over-expression of AKR1B10 has been also observed in other tumors, such as smokers' non-small cell lung carcinomas, 2) uterine carcinomas, 3) cholangiocarcinomas, 4) pancreatic carcinoma, 5) and breast cancer. 6) The silencing of the AKR1B10 gene results in growth inhibition of cancer cells [5][6][7][8] and hepatocellular carcinoma xenografts in mice, 9) and its elevated expression in turn promotes proliferation of cancer cells, 10,11) indicating that the enzyme participates in tumor development.…”

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confidence: 98%

Inhibition of Human Aldose Reductase-Like Protein (AKR1B10) by α- and γ-Mangostins, Major Components of Pericarps of Mangosteen

Soda

Endo

Matsunaga

et al. 2012

Biological & Pharmaceutical Bulletin

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A human member of the aldo-keto reductase (AKR) superfamily, AKR1B10, was recently identified as both diagnostic marker and therapeutic target in the treatment of several types of cancer. In this study, we have examined AKR1B10 inhibition by five xanthone derivatives, components of pericarps of mangosteen, of which α-and γ-mangostins show potential anti-cancer properties. Among the five xanthones, γ-mangostin was found to be the most potent competitive inhibitor (inhibition constant, 5.6 nM), but its 7-methoxy derivative, α-mangostin, was the second potent inhibitor (inhibition constant, 80 nM). Molecular docking of the two mangostins in AKR1B10 and site-directed mutagenesis of the putative binding residues revealed that Phe123, Trp220, Val301 and Gln303 are important for the tight binding of γ-mangostin, and suggested that the 7-methoxy group of α-mangostin impairs the inhibitory potency by altering the orientation of the inhibitor molecule in the substrate-binding site of the enzyme.Key words aldo-keto reductase 1B10; aldose reductase; mangostin; xanthone; anti-cancer property; molecular docking A human member of the aldo-keto reductase (AKR) superfamily, AKR1B10, is a reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reductase, which was originally identified as a human aldose reductase (AKR1B1)-like protein that is up-regulated in hepatocellular carcinomas. 1)Over-expression of AKR1B10 has been also observed in other tumors, such as smokers' non-small cell lung carcinomas, 2) uterine carcinomas, 3) cholangiocarcinomas, 4) pancreatic carcinoma, 5) and breast cancer.6) The silencing of the AKR1B10 gene results in growth inhibition of cancer cells [5][6][7][8] and hepatocellular carcinoma xenografts in mice, 9) and its elevated expression in turn promotes proliferation of cancer cells, 10,11) indicating that the enzyme participates in tumor development. Due to its high catalytic efficiency towards aliphatic aldehydes, retinals and isoprenyl aldehydes, 1,[6][7][8]12,13) the roles suggested for AKR1B10 in cell carcinogenesis and tumor development are detoxification of cytotoxic carbonyls derived from lipid peroxidation, [6][7][8] decrease in retinoic acid synthesis, 12) and modulation of protein prenylation. 6,11,13) In addition, AKR1B10 is suggested to promote fatty acid synthesis in liver cancer cells by blocking the ubiquitin-dependent degradation of acetyl CoA carboxylase. 8) Thus, this enzyme has been recognized not only as a potential diagnostic and/or prognostic marker, but also as a potential therapeutic target for the prevention and treatment of the above types of cancer. However, because of the high structural similarity between AKR1B10 and AKR1B1 that plays distinct roles in glucose and prostaglandin metabolism, 14,15) the selective inhibition of AKR1B10 over AKR1B1 is required for the development of treatments targeting the types of cancer linked to AKR1B10.Synthetic and natural compounds that show inhibitory effects on AKR1B10 have been reported, as reviewed by Matsunaga et al. 1...

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Identification and expression analysis of the aldo–ketoreductase1-B10 gene in primary malignant liver tumours

Cited by 87 publications

References 51 publications

Prognostic significance of AKR1B10 gene expression in hepatocellular carcinoma and surrounding non-tumorous liver tissue

Prognostic significance of AKR1B10 gene expression in hepatocellular carcinoma and surrounding non-tumorous liver tissue

Aldo-Keto Reductase Family 1 Member B10 Inhibitors: Potential Drugs for Cancer Treatment

Inhibition of Human Aldose Reductase-Like Protein (AKR1B10) by α- and γ-Mangostins, Major Components of Pericarps of Mangosteen

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