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Differential gene expression of NAD(P)H:quinone oxidoreductase and NRH:quinone oxidoreductase in human hepatocellular and biliary tissue.
Mol Pharmacol. 2002 Feb; 61(2):320-5.MP

Abstract

NAD(P)H:quinone oxidoreductase (NQO1) and dihydronicotinamide riboside:quinone oxidoreductases (NQO2) are cytosolic flavoproteins that catalyze the two-electron reduction of quinones and quinoid compounds to hydroquinones, thereby promoting detoxification and preventing the formation of highly reactive oxygen species, which lead to DNA and cell damage. Two NQO isoforms, designated NQO1 and NQO2, have been cloned and sequenced. To elucidate their role in carcinogenesis, the gene expression of human NQO1 and NQO2 in paired normal and tumor tissue samples was examined. Quantitative triplex reverse transcriptase polymerase chain reaction was employed to analyze NQO1 and NQO2 mRNA expression in normal hepatic and biliary tissue as well as in cholangiocellular carcinomas (CCC), hepatocellular carcinomas (HCC), and focal nodular hyperplasias (FNH). Coexpression of beta-actin RNA was used as an internal reference standard and linear ranges of transcript amplification were established for each sample. In normal hepatocellular tissue, the two NQO isoforms were differentially regulated, with a higher expression of NQO2 than NQO1. Malignant hepatocellular tissue (HCC), however, displayed up-regulation of NQO1 and down-regulation of NQO2. Regulation of either transcript was not seen in benign hepatocellular tumor tissue (FNH), which indicates a reciprocal control of NQO genes in hepatocarcinogenesis. Normal biliary tissue expressed a significantly higher level of NQO1 transcripts compared with normal liver, whereas biliary NQO2 levels were significantly lower than in hepatocellular tissue. Comparing the levels of expression in normal and malignant biliary tissue (CCC), no significant differences were noted between the expression levels of either transcript. Thus, this study provides evidence for differential hepatic and biliary regulation of both NQO1 and NQO2.

Authors+Show Affiliations

Department of Chemistry, Cancer Center, University of California, San Diego, La Jolla, California 92093-0636, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11809856

Citation

Strassburg, Ahlke, et al. "Differential Gene Expression of NAD(P)H:quinone Oxidoreductase and NRH:quinone Oxidoreductase in Human Hepatocellular and Biliary Tissue." Molecular Pharmacology, vol. 61, no. 2, 2002, pp. 320-5.
Strassburg A, Strassburg CP, Manns MP, et al. Differential gene expression of NAD(P)H:quinone oxidoreductase and NRH:quinone oxidoreductase in human hepatocellular and biliary tissue. Mol Pharmacol. 2002;61(2):320-5.
Strassburg, A., Strassburg, C. P., Manns, M. P., & Tukey, R. H. (2002). Differential gene expression of NAD(P)H:quinone oxidoreductase and NRH:quinone oxidoreductase in human hepatocellular and biliary tissue. Molecular Pharmacology, 61(2), 320-5.
Strassburg A, et al. Differential Gene Expression of NAD(P)H:quinone Oxidoreductase and NRH:quinone Oxidoreductase in Human Hepatocellular and Biliary Tissue. Mol Pharmacol. 2002;61(2):320-5. PubMed PMID: 11809856.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential gene expression of NAD(P)H:quinone oxidoreductase and NRH:quinone oxidoreductase in human hepatocellular and biliary tissue. AU - Strassburg,Ahlke, AU - Strassburg,Christian P, AU - Manns,Michael P, AU - Tukey,Robert H, PY - 2002/1/26/pubmed PY - 2002/2/8/medline PY - 2002/1/26/entrez SP - 320 EP - 5 JF - Molecular pharmacology JO - Mol Pharmacol VL - 61 IS - 2 N2 - NAD(P)H:quinone oxidoreductase (NQO1) and dihydronicotinamide riboside:quinone oxidoreductases (NQO2) are cytosolic flavoproteins that catalyze the two-electron reduction of quinones and quinoid compounds to hydroquinones, thereby promoting detoxification and preventing the formation of highly reactive oxygen species, which lead to DNA and cell damage. Two NQO isoforms, designated NQO1 and NQO2, have been cloned and sequenced. To elucidate their role in carcinogenesis, the gene expression of human NQO1 and NQO2 in paired normal and tumor tissue samples was examined. Quantitative triplex reverse transcriptase polymerase chain reaction was employed to analyze NQO1 and NQO2 mRNA expression in normal hepatic and biliary tissue as well as in cholangiocellular carcinomas (CCC), hepatocellular carcinomas (HCC), and focal nodular hyperplasias (FNH). Coexpression of beta-actin RNA was used as an internal reference standard and linear ranges of transcript amplification were established for each sample. In normal hepatocellular tissue, the two NQO isoforms were differentially regulated, with a higher expression of NQO2 than NQO1. Malignant hepatocellular tissue (HCC), however, displayed up-regulation of NQO1 and down-regulation of NQO2. Regulation of either transcript was not seen in benign hepatocellular tumor tissue (FNH), which indicates a reciprocal control of NQO genes in hepatocarcinogenesis. Normal biliary tissue expressed a significantly higher level of NQO1 transcripts compared with normal liver, whereas biliary NQO2 levels were significantly lower than in hepatocellular tissue. Comparing the levels of expression in normal and malignant biliary tissue (CCC), no significant differences were noted between the expression levels of either transcript. Thus, this study provides evidence for differential hepatic and biliary regulation of both NQO1 and NQO2. SN - 0026-895X UR - https://www.unboundmedicine.com/medline/citation/11809856/Differential_gene_expression_of_NAD_P_H:quinone_oxidoreductase_and_NRH:quinone_oxidoreductase_in_human_hepatocellular_and_biliary_tissue_ L2 - http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=11809856 DB - PRIME DP - Unbound Medicine ER -