Deficiency of multidrug resistance 2 contributes to cell transformation through oxidative stress.

Abstract:

:Multidrug resistance 2 (Mdr2), also called adenosine triphosphate-binding cassette B4 (ABCB4), is the transporter of phosphatidylcholine (PC) at the canalicular membrane of mouse hepatocytes, which plays an essential role for bile formation. Mutations in human homologue MDR3 are associated with several liver diseases. Knockout of Mdr2 results in hepatic inflammation, liver fibrosis and hepatocellular carcinoma (HCC). Whereas the pathogenesis in Mdr2 (-/-) mice has been largely attributed to the toxicity of bile acids due to the absence of PC in the bile, the question of whether Mdr2 deficiency per se perturbs biological functions in the cell has been poorly addressed. As Mdr2 is expressed in many cell types, we used mouse embryonic fibroblasts (MEF) derived from Mdr2 (-/-) embryos to show that deficiency of Mdr2 increases reactive oxygen species accumulation, lipid peroxidation and DNA damage. We found that Mdr2 (-/-) MEFs undergo spontaneous transformation and that Mdr2 (-/-) mice are more susceptible to chemical carcinogen-induced intestinal tumorigenesis. Microarray analysis in Mdr2-/- MEFs and cap analysis of gene expression in Mdr2 (-/-) HCCs revealed extensively deregulated genes involved in oxidation reduction, fatty acid metabolism and lipid biosynthesis. Our findings imply a close link between Mdr2 (-/-) -associated tumorigenesis and perturbation of these biological processes and suggest potential extrahepatic functions of Mdr2/MDR3.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Tebbi A,Levillayer F,Jouvion G,Fiette L,Soubigou G,Varet H,Boudjadja N,Cairo S,Hashimoto K,Suzuki AM,Carninci P,Carissimo A,di Bernardo D,Wei Y

doi

10.1093/carcin/bgv156

subject

Has Abstract

pub_date

2016-01-01 00:00:00

pages

39-48

issue

1

eissn

0143-3334

issn

1460-2180

pii

bgv156

journal_volume

37

pub_type

杂志文章
  • DNA polymerase, RNA polymerase and exonuclease activities on a DNA sequence modified by benzo[a]pyrene diolepoxide.

    abstract::Adducts produced by modification of DNA with benzo[a]pyrene diolepoxide (BPDE) are known to inhibit both DNA and RNA synthesis. This phenomenon has been used as a method for determining the distribution of carcinogen binding within defined DNA sequences. A critical comparison of different enzyme activities on adducted...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/13.9.1529

    authors: Thrall BD,Mann DB,Smerdon MJ,Springer DL

    更新日期:1992-09-01 00:00:00

  • Green tea polyphenol (-)-epigallocatechin-3-gallate treatment of human skin inhibits ultraviolet radiation-induced oxidative stress.

    abstract::The use of naturally occurring botanicals with substantial antioxidant activity to afford protection to human skin against UV damage is receiving increasing attention. The green tea constituent (-)-epigallocatechin-3-gallate (EGCG) is a potent antioxidant and has shown remarkable preventive effects against photocarcin...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/22.2.287

    authors: Katiyar SK,Afaq F,Perez A,Mukhtar H

    更新日期:2001-02-01 00:00:00

  • Polymorphisms in glutathione S-transferases and non-melanoma skin cancer risk in Australian renal transplant recipients.

    abstract::Caucasian renal transplant recipients from Queensland, Australia have the highest non-melanoma skin cancer (NMSC) risk worldwide. Although ultraviolet light (UVR) exposure is critical, genetic factors also appear important. We and others have shown that polymorphism in the glutathione S-transferases (GST) is associate...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgh291

    authors: Fryer AA,Ramsay HM,Lovatt TJ,Jones PW,Hawley CM,Nicol DL,Strange RC,Harden PN

    更新日期:2005-01-01 00:00:00

  • GBP-1 acts as a tumor suppressor in colorectal cancer cells.

    abstract::The human guanylate-binding protein 1 (GBP-1) is among the proteins the most highly induced by interferon-γ (IFN-γ) in every cell type investigated as yet. In vivo, GBP-1 expression is associated with the presence of inflammation and has been observed in autoimmune diseases, inflammatory bowel diseases (IBD) and cance...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgs310

    authors: Britzen-Laurent N,Lipnik K,Ocker M,Naschberger E,Schellerer VS,Croner RS,Vieth M,Waldner M,Steinberg P,Hohenadl C,Stürzl M

    更新日期:2013-01-01 00:00:00

  • Effects of temporary selenium supplementation on the genesis of spontaneous mammary tumors in inbred female C3H/St mice.

    abstract::Female inbred C3H/St mice infected with the Bittner Milk Particle, develop mammary adenocarcinoma with 27% incidence if maintained on a Torula Yeast diet supplemented with 1 ppm of selenium (organically bound, in yeast). Animals switched from the 1 ppm Se diet to a diet containing only 0.15 ppm Se after reaching the a...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/1.2.199

    authors: Schrauzer GN,McGinness JE,Kuehn K

    更新日期:1980-02-01 00:00:00

  • The effects of alternating dietary restriction and ad libitum feeding of mice on the development of diethylnitrosamine-induced liver tumours and its correlation to insulinaemia.

    abstract::The effects of alternating ad libitum feeding and 30% restriction of the dietary intake on the development of diethylnitrosamine (DEN)-induced hepatic neoplasia were investigated. Dietary restriction retarded the growth of glucose-6-phosphatase-deficient (G6Pd) preneoplastic foci and subsequently that of hepatocellula...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/12.2.311

    authors: Lagopoulos L,Sunahara GI,Würzner H,Dombrowsky I,Stalder R

    更新日期:1991-02-01 00:00:00

  • Tissue levels of S-adenosylmethionine and S-adenosylhomocysteine in rats fed methyl-deficient, amino acid-defined diets for one to five weeks.

    abstract::The levels of S-adenosylmethionine (AdoMet) and of S-adenosylhomocysteine (AdoHcy) as well as the ratio of AdoMet/AdoHcy were determined in the liver, lungs, testes and kidneys of weanling male rats fed a commercial chow diet or 5 different amino acid-defined diets for 1-5 weeks. The amino acid-defined diets used were...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/4.8.1051

    authors: Shivapurkar N,Poirier LA

    更新日期:1983-08-01 00:00:00

  • Decorin-mediated inhibition of colorectal cancer growth and migration is associated with E-cadherin in vitro and in mice.

    abstract::Previous studies have shown that decorin expression is significantly reduced in colorectal cancer tissues and cancer cells, and genetic deletion of the decorin gene is sufficient to cause intestinal tumor formation in mice, resulting from a downregulation of p21, p27(kip1) and E-cadherin and an upregulation of β-caten...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgr293

    authors: Bi X,Pohl NM,Qian Z,Yang GR,Gou Y,Guzman G,Kajdacsy-Balla A,Iozzo RV,Yang W

    更新日期:2012-02-01 00:00:00

  • Slc10a2-null mice uncover colon cancer-promoting actions of endogenous fecal bile acids.

    abstract::Although epidemiological evidence in humans and bile acid feeding studies in rodents implicate bile acids as tumor promoters, the role of endogenous bile acids in colon carcinogenesis remains unclear. In this study, we exploited mice deficient in the ileal apical sodium-dependent bile acid transporter (ASBT, encoded b...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgv107

    authors: Raufman JP,Dawson PA,Rao A,Drachenberg CB,Heath J,Shang AC,Hu S,Zhan M,Polli JE,Cheng K

    更新日期:2015-10-01 00:00:00

  • Effects of glucose on the formation of PhIP in a model system.

    abstract::The effect of glucose on the formation of the food mutagen PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) was studied in a model system. When a mixture of creatine (0.9 mmol), phenylalanine (0.9 mmol) and glucose (0.45 mmol) was heated in diethylene glycol and water (3 ml, 5:1) for 10 min at 180 or 225 degrees...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/12.12.2297

    authors: Skog K,Jägerstad M

    更新日期:1991-12-01 00:00:00

  • Tocopherols inhibit estrogen-induced cancer stemness and OCT4 signaling in breast cancer.

    abstract::Estrogen plays an important role in breast cancer development. While the mechanism of the estrogen effects is not fully elucidated, one possible route is by increasing the stem cell-like properties in the tumors. Tocopherols are known to reduce breast cancer development and progression. The aim of the present study is...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgy071

    authors: Bak MJ,Furmanski P,Shan NL,Lee HJ,Bao C,Lin Y,Shih WJ,Yang CS,Suh N

    更新日期:2018-07-30 00:00:00

  • The benzamide derivative metoclopramide causes DNA damage and inhibition of DNA repair in human peripheral mononuclear leukocytes at clinically relevant doses.

    abstract::The polysubstituted benzamide derivative metoclopramide (MCA) has previously been shown to enhance the effect of cisplatin and ionizing radiation treatment of xenografted human squamous cell carcinomas from the head and neck region. In the present work we show that MCA decreases the nucleoid sedimentation rate, indica...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/12.9.1613

    authors: Lybak S,Pero RW

    更新日期:1991-09-01 00:00:00

  • The principal urinary metabolite of allyl isothiocyanate, N-acetyl-S-(N-allylthiocarbamoyl)cysteine, inhibits the growth and muscle invasion of bladder cancer.

    abstract::Naturally occurring allyl isothiocyanate (AITC) was recently shown to be selectively delivered to bladder cancer tissue via urinary excretion and to inhibit bladder cancer growth and muscle invasion in an animal model. AITC is excreted in urine mainly as N-acetyl-S-(N-allylthiocarbamoyl)cysteine, more commonly known a...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgr283

    authors: Bhattacharya A,Li Y,Geng F,Munday R,Zhang Y

    更新日期:2012-02-01 00:00:00

  • Partial hepatectomy is a promoter of hepatocarcinogenesis in C57BL/6J male mice but not in C3H/HeJ male mice.

    abstract::We have shown previously that the difference between C57BL/6J and C3H/HeJ male mice in their susceptibilities to chemically-induced liver tumors results predominantly from an allelic difference at the Hepatocarcinogen sensitivity (Hcs) locus. This locus modulates the rate of growth of preneoplastic liver lesions and m...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/11.4.589

    authors: Hanigan MH,Winkler ML,Drinkwater NR

    更新日期:1990-04-01 00:00:00

  • Upregulation of CYP1B1 expression by inflammatory cytokines is mediated by the p38 MAP kinase signal transduction pathway.

    abstract::Cytochrome P450 1B1 (CYP1B1) is an enzyme that has a unique tumor-specific pattern of expression and is capable of bioactivating a wide range of carcinogenic compounds. We have reported previously that coordinated upregulation of CYP1B1 by inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and the aryl hy...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgu190

    authors: Smerdová L,Šmerdová J,Kabátková M,Kohoutek J,Blažek D,Machala M,Vondráček J

    更新日期:2014-11-01 00:00:00

  • Prevention of dual promoting effects of pentachlorophenol, an environmental pollutant, on diethylnitrosamine-induced hepato- and cholangiocarcinogenesis in mice by green tea infusion.

    abstract::In order to explore a possibility that the custom of drinking green tea infusion is efficacious for reducing the carcinogenic risk of environmental exposure to pentachlorophenol (PCP), we examined the effects in a hepato- and cholangiocarcinogenesis model in mice exposed to diethylnitrosamine (DEN). In the first exper...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgg053

    authors: Umemura T,Kai S,Hasegawa R,Kanki K,Kitamura Y,Nishikawa A,Hirose M

    更新日期:2003-06-01 00:00:00

  • Genetic variations in the transforming growth factor-beta pathway as predictors of survival in advanced non-small cell lung cancer.

    abstract::The magnitude of benefit is variable for advanced non-small cell lung cancer (NSCLC) patients receiving platinum-based chemotherapy. The purpose of this study is to determine whether genetic variations in the transforming growth factor-beta (TGF-β) pathway are associated with clinical outcomes in NSCLC patients receiv...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgr067

    authors: Lin M,Stewart DJ,Spitz MR,Hildebrandt MA,Lu C,Lin J,Gu J,Huang M,Lippman SM,Wu X

    更新日期:2011-07-01 00:00:00

  • Genetic modifiers of carcinogen DNA adducts in target lung and peripheral blood mononuclear cells.

    abstract::Measurement of carcinogen DNA adducts in blood has been used as a surrogate for the target lung tissue. We aimed to examine whether genetic polymorphisms in several metabolic pathway genes modify the relation between DNA adducts in target lung and blood. One hundred and thirty-five early-stage lung cancer patients fro...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgq208

    authors: Lee MS,Su L,Mark EJ,Wain JC,Christiani DC

    更新日期:2010-12-01 00:00:00

  • Docosahexaenoic acid alters epidermal growth factor receptor-related signaling by disrupting its lipid raft association.

    abstract::Docosahexaenoic acid (DHA), a 22:6 n-3 polyunsaturated fatty acid, is the longest and most highly unsaturated fatty acid found in most membranes and has been shown to inhibit cancer cell growth in part by modifying cell signaling. In the current study, alterations to epidermal growth factor receptor (EGFR) signaling u...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgq111

    authors: Rogers KR,Kikawa KD,Mouradian M,Hernandez K,McKinnon KM,Ahwah SM,Pardini RS

    更新日期:2010-09-01 00:00:00

  • Epigenetic silencing of DKK2 and Wnt signal pathway components in human ovarian carcinoma.

    abstract::Wnt/β-Catenin signaling dysregulation is involved in tumorigenesis. Furthermore, epigenetic modification of the Dickkopf (DKK) family (DKK1-DKK4) has been shown to be important in Wnt signaling regulation. In this study, the role of DKK2, a Wnt antagonist, in epithelial ovarian cancer (EOC) was evaluated by examining ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgs278

    authors: Zhu J,Zhang S,Gu L,Di W

    更新日期:2012-12-01 00:00:00

  • LIFR functions as a metastasis suppressor in hepatocellular carcinoma by negatively regulating phosphoinositide 3-kinase/AKT pathway.

    abstract::Hepatocellular carcinoma (HCC) is one of the leading causes for cancer related mortality worldwide. Poor prognosis of HCC patients is mainly due to frequent metastasis and recurrence. Deregulation of metastasis suppressors in malignant cells plays critical roles during cancer metastasis. Thus, novel metastasis suppres...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgv108

    authors: Luo Q,Wang C,Jin G,Gu D,Wang N,Song J,Jin H,Hu F,Zhang Y,Ge T,Huo X,Chu W,Shu H,Fang J,Yao M,Gu J,Cong W,Qin W

    更新日期:2015-10-01 00:00:00

  • The redox protein thioredoxin-1 regulates the constitutive and inducible expression of the estrogen metabolizing cytochromes P450 1B1 and 1A1 in MCF-7 human breast cancer cells.

    abstract::The oxidative metabolites of estrogen have been proposed to play an important role in the development of some human cancers. The two major pathways of estrogen metabolism, to the carcinogenic 4-hydroxyestradiol (4-OHE2) and to the non-carcinogenic 2-hydroxyestradiol (2-OHE2), are mediated by cytochromes P450 CYP1B1 an...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/23.10.1625

    authors: Husbeck B,Powis G

    更新日期:2002-10-01 00:00:00

  • Metabolic reprogramming and dysregulated metabolism: cause, consequence and/or enabler of environmental carcinogenesis?

    abstract::Environmental contributions to cancer development are widely accepted, but only a fraction of all pertinent exposures have probably been identified. Traditional toxicological approaches to the problem have largely focused on the effects of individual agents at singular endpoints. As such, they have incompletely addres...

    journal_title:Carcinogenesis

    pub_type: 杂志文章,评审

    doi:10.1093/carcin/bgv037

    authors: Robey RB,Weisz J,Kuemmerle NB,Salzberg AC,Berg A,Brown DG,Kubik L,Palorini R,Al-Mulla F,Al-Temaimi R,Colacci A,Mondello C,Raju J,Woodrick J,Scovassi AI,Singh N,Vaccari M,Roy R,Forte S,Memeo L,Salem HK,Amedei A,

    更新日期:2015-06-01 00:00:00

  • The Notch signaling pathway as a mediator of tumor survival.

    abstract::The Notch signaling pathway is evolutionarily conserved and responsible for cell fate determination in the developing embryo and mature tissue. At the molecular level, ligand binding activates Notch signaling by liberating the Notch intracellular domain, which then translocates into the nucleus and activates gene tran...

    journal_title:Carcinogenesis

    pub_type: 杂志文章,评审

    doi:10.1093/carcin/bgt127

    authors: Capaccione KM,Pine SR

    更新日期:2013-07-01 00:00:00

  • Inhibition of UV light- and Fenton reaction-induced oxidative DNA damage by the soybean isoflavone genistein.

    abstract::We have investigated the effect of the soybean isoflavone genistein on 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation in calf thymus DNA exposed to either UV irradiation or the Fenton reaction system. Under the conditions used we observed that UV light and the Fenton reaction significantly increase 8-OHdG formation in...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/17.1.73

    authors: Wei H,Cai Q,Rahn RO

    更新日期:1996-01-01 00:00:00

  • Genetic associations with sporadic neuroendocrine tumor risk.

    abstract::Genetic risk factors for sporadic neuroendocrine tumors (NET) are poorly understood. We tested risk associations in patients with sporadic NET and non-cancer controls, using a custom array containing 1536 single-nucleotide polymorphisms (SNPs) in 355 candidate genes. We identified 18 SNPs associated with NET risk at a...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgr095

    authors: Ter-Minassian M,Wang Z,Asomaning K,Wu MC,Liu CY,Paulus JK,Liu G,Bradbury PA,Zhai R,Su L,Frauenhoffer CS,Hooshmand SM,De Vivo I,Lin X,Christiani DC,Kulke MH

    更新日期:2011-08-01 00:00:00

  • Curcumin inhibits COPD-like airway inflammation and lung cancer progression in mice.

    abstract::Recent studies have demonstrated that K-ras mutations in lung epithelial cells elicit inflammation that promotes carcinogenesis in mice (intrinsic inflammation). The finding that patients with chronic obstructive pulmonary disease (COPD), an inflammatory disease of the lung, have an increased risk of lung cancer after...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgp229

    authors: Moghaddam SJ,Barta P,Mirabolfathinejad SG,Ammar-Aouchiche Z,Garza NT,Vo TT,Newman RA,Aggarwal BB,Evans CM,Tuvim MJ,Lotan R,Dickey BF

    更新日期:2009-11-01 00:00:00

  • Esterification of all-trans-retinol in normal human epithelial cell strains and carcinoma lines from oral cavity, skin and breast: reduced expression of lecithin:retinol acyltransferase in carcinoma lines.

    abstract::When exogenous [(3)H]retinol (vitamin A) was added to culture medium, normal human epithelial cells from the oral cavity, skin, lung and breast took up and esterified essentially all of the [(3)H]retinol within a few hours. As shown by [(3)H]retinol pulse-chase experiments, normal epithelial cells then slowly hydrolyz...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/21.11.1925

    authors: Guo X,Ruiz A,Rando RR,Bok D,Gudas LJ

    更新日期:2000-11-01 00:00:00

  • Bay-region distortions in a methanol adduct of a bay-region diol epoxide of the carcinogen 5-methylchrysene.

    abstract::The three-dimensional structure of the product of the reaction of a diol epoxide of the carcinogen 5-methylchrysene with methanol has been determined by an X-ray diffraction analysis. The diol epoxide used to obtain this compound contains a stereochemically hindered bay region because of the location of the 5-methyl g...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/17.11.2507

    authors: Afshar CE,Carrell CJ,Carrell HL,Harvey RG,Kiselyov AS,Amin S,Glusker JP

    更新日期:1996-11-01 00:00:00

  • HPV+ Oropharyngeal Squamous Cell Carcinomas from patients with two tumors display synchrony of viral genomes yet discordant mutational profiles and signatures.

    abstract::Human Papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma (HPV+OPSCC) is increasing in prevalence in the United States, as are cases of patients with multiple HPV+OPSCCs (mHPV+OPSCC). mHPV+OPSCCs present a unique opportunity to examine HPV+OPSCC mutation acquisition and evolution. We performed sequenci...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgaa111

    authors: Faden DL,Langenbucher A,Kuhs K,Lewis JS,Mirabello L,Yeager M,Boland JF,Bass S,Steinberg M,Cullen M,Lawrence MS,Ferris RL

    更新日期:2020-10-19 00:00:00