CpG methylation-dependent repression of the human O6-methylguanine-DNA methyltransferase gene linked to chromatin structure alteration.

Abstract:

:The mechanism of inactivation of the O6-methylguanine-DNA methyltransferase (MGMT), responsible for repair of mutagenic and cytotoxic O6-alkylguanine, in Mex- tumor cells, is not completely understood. We have examined the role of CpG methylation in the human MGMT promoter in a luciferase (luc) reporter plasmid and associated alteration in chromatin structure. Methylation of 16% CpG sequences in promoter and flanking sequences in the plasmid with HpaII methylase reduced luciferase activity by 10-12-fold, while methylation of all CpG sites, including those in the luc coding sequence, as well as the promoter sequence blocked expression completely. Repression of luc expression due to partial but not complete CpG methylation could be reversed by histone deacetylase inhibitor trichostatin A (TSA). However, 5-azacytidine, which reverses CpG methylation, but not TSA, could reactivate silent MGMT gene in Mex- HeLa MR cells. Furthermore, chromatin immunoprecipitation (ChIP) assay showed reduced level of acetylation of H4 histone bound to the methylated promoter compared with the non-methylated promoter. These results suggest that complete repression of the MGMT gene in Mex- cells requires methylation of CpG sequences in both promoter and neighboring regions of the gene, resulting in inactive, condensed chromatin state of the gene.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Bhakat KK,Mitra S

doi

10.1093/carcin/bgg086

keywords:

subject

Has Abstract

pub_date

2003-08-01 00:00:00

pages

1337-45

issue

8

eissn

0143-3334

issn

1460-2180

pii

bgg086

journal_volume

24

pub_type

杂志文章
  • Extra-virgin olive oil contains a metabolo-epigenetic inhibitor of cancer stem cells.

    abstract::Targeting tumor-initiating, drug-resistant populations of cancer stem cells (CSC) with phytochemicals is a novel paradigm for cancer prevention and treatment. We herein employed a phenotypic drug discovery approach coupled to mechanism-of-action profiling and target deconvolution to identify phenolic components of ext...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgy023

    authors: Corominas-Faja B,Cuyàs E,Lozano-Sánchez J,Cufí S,Verdura S,Fernández-Arroyo S,Borrás-Linares I,Martin-Castillo B,Martin ÁG,Lupu R,Nonell-Canals A,Sanchez-Martinez M,Micol V,Joven J,Segura-Carretero A,Menendez JA

    更新日期:2018-04-05 00:00:00

  • Absence of regular alpha2(I) collagen chains in colon carcinoma biopsy fragments.

    abstract::The extracellular matrix (ECM) is known to play an active role in numerous biological processes such as differentiation, apoptosis and cancer. Extensive alterations of epithelial basement membranes and of interstitial ECM are known to occur during the progression of most invasive carcinomas. Collagen, which represents...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/19.4.575

    authors: Pucci-Minafra I,Andriolo M,Basiricò L,Alessandro R,Luparello C,Buccellato C,Garbelli R,Minafra S

    更新日期:1998-04-01 00:00:00

  • Oral microbial dysbiosis and its performance in predicting oral cancer.

    abstract::Dysbiosis of oral microbiome may dictate the progression of oral squamous cell carcinoma (OSCC). Yet, the composition of oral microbiome fluctuates by saliva and distinct sites of oral cavity and is affected by risky behaviors (smoking, drinking, and betel quid chewing) and individuals' oral health condition. To chara...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgaa062

    authors: Su SC,Chang LC,Huang HD,Peng CY,Chuang CY,Chen YT,Lu MY,Chiu YW,Chen PY,Yang SF

    更新日期:2020-07-04 00:00:00

  • Effect of cAMP elevating compounds on inhibition of gap junctional communication and induction of morphological transformation in Syrian hamster embryo cells.

    abstract::An enhancement of the cellular cAMP level has been shown to protect against phorbol ester-induced inhibition of gap junctional intercellular communication (GJIC) and induction of morphological transformation in Syrian hamster embryo (SHE) cells. Cholera toxin, forskolin, 3-isobutyl-1-methylxanthine (IBMX) and theophyl...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/13.10.1803

    authors: Roseng LE,Rivedal E,Sanner T

    更新日期:1992-10-01 00:00:00

  • Superoxide generation from Kupffer cells contributes to hepatocarcinogenesis: studies on NADPH oxidase knockout mice.

    abstract::We hypothesized that superoxide from Kupffer cells (KC) contributes to hepatocarcinogenesis. p47phox(-/-) mice, deficient in phagocyte NADPH oxidase and superoxide generation, received a single dose of the hepatocarcinogen diethylnitrosamine (DEN). The following hepatic effects were observed at time points between 30 ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgh320

    authors: Teufelhofer O,Parzefall W,Kainzbauer E,Ferk F,Freiler C,Knasmüller S,Elbling L,Thurman R,Schulte-Hermann R

    更新日期:2005-02-01 00:00:00

  • Generation of S phase-dependent DNA double-strand breaks by Cr(VI) exposure: involvement of ATM in Cr(VI) induction of gamma-H2AX.

    abstract::Certain hexavalent chromium [Cr(VI)] compounds are implicated as occupational respiratory carcinogens. Cr(VI) induces a broad spectrum of DNA damage, but Cr(VI)-induced DNA double-strand breaks (DSBs) have not been reported. Previously we found that Cr(VI) activates the ataxia telangiectasia mutated (ATM) kinase. ATM ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgh242

    authors: Ha L,Ceryak S,Patierno SR

    更新日期:2004-11-01 00:00:00

  • Nitrosation by stimulated macrophages. Inhibitors, enhancers and substrates.

    abstract::Macrophages and their immortalized cell lines can be activated to form nitrite and nitrate via oxidation of arginine and this is accompanied by the formation of N-nitroso compounds. The mechanism of nitrosamine formation has been investigated through the use of compounds which are known either to inhibit or enhance ac...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/10.3.563

    authors: Kosaka H,Wishnok JS,Miwa M,Leaf CD,Tannenbaum SR

    更新日期:1989-03-01 00:00:00

  • Met receptor tyrosine kinase transactivation is involved in proteinase-activated receptor-2-mediated hepatocellular carcinoma cell invasion.

    abstract::The expression of proteinase-activated receptor (PAR)(2) in human hepatocellular carcinoma (HCC) was established by reverse transcription-polymerase chain reaction, confocal immunofluorescence and electron microscopy in permanent cell lines, primary HCC cell cultures and HCC tumor tissue. Stimulation of HCC cells with...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgp153

    authors: Kaufmann R,Oettel C,Horn A,Halbhuber KJ,Eitner A,Krieg R,Katenkamp K,Henklein P,Westermann M,Böhmer FD,Ramachandran R,Saifeddine M,Hollenberg MD,Settmacher U

    更新日期:2009-09-01 00:00:00

  • Steroid hormone receptor expression and proliferation in rat mammary gland carcinomas induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.

    abstract::2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mammary gland carcinogen present in the human diet. Herein, the expression of estrogen receptor alpha (ERalpha), estrogen receptor beta (ER beta) and progesterone receptor (PR) was examined in mammary gland carcinomas induced by PhIP in female Sprague-Dawley ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgi013

    authors: Qiu C,Shan L,Yu M,Snyderwine EG

    更新日期:2005-04-01 00:00:00

  • Nitric oxide induces cyclooxygenase expression and inhibits cell growth in colon cancer cell lines.

    abstract::The role of nitric oxide (NO) in colon cancer remains controversial. Inducible nitric oxide synthase (iNOS) has been reported to be up regulated and down regulated in colorectal cancer in both animal models and patient tissue samples. Cyclooxygenase-2 (COX-2) is important in colorectal carcinogenesis but its relations...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgg014

    authors: Liu Q,Chan ST,Mahendran R

    更新日期:2003-04-01 00:00:00

  • Aromatic DNA adducts, micronuclei and genetic polymorphism for CYP1A1 and GST1 in chimney sweeps.

    abstract::Aromatic DNA adducts in total white blood cells, cytochrome P450 (CYP) class 1A1 and glutathione transferase (GST1) class mu genotypes and micronuclei in T- and B-lymphocytes were studied in 69 full-time chimney sweeps and 35 controls, all male subjects. The sweeps had a higher (22%) but statistically non-significant ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/15.7.1347

    authors: Ichiba M,Hagmar L,Rannug A,Högstedt B,Alexandrie AK,Carstensen U,Hemminki K

    更新日期:1994-07-01 00:00:00

  • Effects of ethinyl estradiol and tamoxifen on liver DNA turnover and new synthesis and appearance of gamma glutamyl transpeptidase-positive foci in female rats.

    abstract::We investigated possible mechanisms associated with promotion of hepatocarcinogenesis by the synthetic estrogens mestranol (M) and ethinyl estradiol (EE). Our first objective was to determine whether chronic EE treatment was associated with hepatotoxicity accompanied by regenerative hyperplasia. Female Sprague-Dawley ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/7.12.2007

    authors: Yager JD,Roebuck BD,Paluszcyk TL,Memoli VA

    更新日期:1986-12-01 00:00:00

  • Genetic polymorphisms of glutathione S-transferases as modulators of lung cancer susceptibility.

    abstract::Some of the glutathione S-transferases (GSTs) are polymorphic and may play a role in lung cancer susceptibility. Our previous study in a French Caucasian study population suggested GSTM1 null genotype as a moderate risk factor for lung cancer. Here we extended the study to investigate the potential role of GSTT1 and G...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/23.9.1475

    authors: Stücker I,Hirvonen A,de Waziers I,Cabelguenne A,Mitrunen K,Cénée S,Koum-Besson E,Hémon D,Beaune P,Loriot MA

    更新日期:2002-09-01 00:00:00

  • Estrogen-responsive RING finger mRNA induction in gastrointestinal carcinoma cells following bile acid treatment.

    abstract::The underlying molecular mechanisms of the tumor-promoting activity of bile acids such as chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) and the protective effect of ursodeoxycholic acid (UDCA) remain largely unclear. Using RNA arbitrarily primed PCR (RAP-PCR) for differential display, we identified, cloned a...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/19.11.1901

    authors: Jung B,Vogt T,Mathieu-Daudé F,Welsh J,McClelland M,Trenkle T,Weitzel C,Kullmann F

    更新日期:1998-11-01 00:00:00

  • Altered tRNA methylation in rats and mice fed lipotrope-deficient diets.

    abstract::A diet that is deficient in methionine, choline, folic acid and vitamin B12 has been found to induce alterations rapidly in liver tRNA methylation in male Fischer rats. In vitro assays indicated that activity of N2-guanine tRNA methyltransferase II (NMG2) was increased to 150% of controls levels in 1 week and 300% of ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/7.3.473

    authors: Wainfan E,Dizik M,Hluboky M,Balis ME

    更新日期:1986-03-01 00:00:00

  • The oncogene LRF is a survival factor in chondrosarcoma and contributes to tumor malignancy and drug resistance.

    abstract::Chondrosarcoma is a form of malignant skeletal tumor of cartilaginous origin. The non-malignant form of the disease is termed chondroma. Correctly distinguishing between the two forms is essential for making therapeutic decisions. However, due to their similar histological appearances and the lack of a reliable diagno...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgs254

    authors: Kumari R,Li H,Haudenschild DR,Fierro F,Carlson CS,Overn P,Gupta L,Gupta K,Nolta J,Yik JH,Di Cesare PE

    更新日期:2012-11-01 00:00:00

  • N-Acetyltransferase 2 polymorphisms, cigarette smoking and alcohol consumption, and oral squamous cell cancer risk.

    abstract::The risk of squamous cell cancers of the oral cavity (OSCC) is strongly related to the use of tobacco and alcohol. N-Acetyl transferases 1 and 2 (NAT2) metabolize aryl- and heterocyclic amines that are present in tobacco smoke. NAT2 slow acetylator phenotype or genotype is related to reduced ability to detoxify these ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/22.12.1993

    authors: Chen C,Ricks S,Doody DR,Fitzgibbons ED,Porter PL,Schwartz SM

    更新日期:2001-12-01 00:00:00

  • Artifactual nitrosation in the lung perfusion apparatus.

    abstract::Teflon tubing used in the isolated, ventilated and perfused lung apparatus (IVPL) was found to yield artifactually high values for nitrosamine formation after it had been exposed to nitrite. In contrast to an earlier report, we found that submilligram levels of nitrite do not react to form significant quantities of ni...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/7.5.845

    authors: Cooney RV,Ross PD,Bartolini GL

    更新日期:1986-05-01 00:00:00

  • Genetic polymorphisms of MPO, COMT, MnSOD, NQO1, interactions with environmental exposures and bladder cancer risk.

    abstract::Tobacco smoking and occupational exposure are major risk factors of bladder cancer via exposure to polycyclic aromatic hydrocarbons (PAHs) and aromatic amines, which lead to oxidative stress and DNA damage. Several enzymes, which play key roles in oxidative stress are polymorphic in humans. Myeloperoxidase (MPO) produ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgh080

    authors: Hung RJ,Boffetta P,Brennan P,Malaveille C,Gelatti U,Placidi D,Carta A,Hautefeuille A,Porru S

    更新日期:2004-06-01 00:00:00

  • Phenotypic expression of carcinogen-initiated epidermal cells to tumor cells by 12-O-tetradecanoylphorbol-13-acetate in a manner dependent on 3T3 fibroblast-derived humoral factor(s).

    abstract::Primary cultured newborn mouse epidermal cells cultured in the low Ca2+ (0.02 mM) medium showed typical basal cell morphology and proliferated as a monolayer. A stepwise increase in medium Ca2+ concentration induced terminal differentiation of epidermal cells. In the case of epidermal cells obtained from newborn mice ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/13.8.1301

    authors: Wang JC,Yamamoto S,Kato R

    更新日期:1992-08-01 00:00:00

  • HTLV-1 bZIP factor impedes the menin tumor suppressor and upregulates JunD-mediated transcription of the hTERT gene.

    abstract::Telomerase activity in cancer cells is dependent on the transcriptional regulation of the human telomerase reverse transcriptase (hTERT) gene, encoding the catalytic subunit of human telomerase. We have shown previously that HTLV-1 basic leucine zipper (HBZ), a viral regulatory protein encoded by the human retrovirus,...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgt221

    authors: Borowiak M,Kuhlmann AS,Girard S,Gazzolo L,Mesnard JM,Jalinot P,Dodon MD

    更新日期:2013-11-01 00:00:00

  • Induction of the aromatic hydrocarbon receptor by trans-4-acetylaminostilbene in rat liver. Comparison with other aromatic amines.

    abstract::The effect of the aromatic amines 2-acetylaminofluorene (AAF), 2-acetylaminophenanthrene (AAP) and trans-4-acetylaminostilbene (AAS) on the rat hepatic aromatic hydrocarbon (Ah) receptor level was studied. 3-Methylcholanthrene (MC), as a known receptor ligand, was used as a control. The complete liver carcinogen AAF a...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/8.7.1021

    authors: Göttlicher M,Cikryt P

    更新日期:1987-07-01 00:00:00

  • Simple methods for quantifying mutagenic heterocyclic aromatic amines in food products.

    abstract::Two solid-phase extraction methods were developed for the determination of mutagenic heterocyclic aromatic amines in heated meat products. The copper phthalocyanine (CPC) tandem extraction was performed on coupled cartridges of diatomaceous earth and CPC-derivatized Sephasorb HP, followed by further clean-up on Sephas...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/11.9.1597

    authors: Gross GA

    更新日期:1990-09-01 00:00:00

  • Differential transformation efficiency but not AP-1 induction under anchorage-dependent and -independent conditions.

    abstract::The JB6 mouse epidermal cell system has been extensively used as an in vitro model for the study of tumor promotion. The present study aimed to assess the relevance of monolayer measurements to the process of transformation, which is induced more efficiently under anchorage-independent (AI) conditions. Although it wou...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/15.5.1001

    authors: Dong Z,Cmarik JL,Wendel EJ,Colburn NH

    更新日期:1994-05-01 00:00:00

  • Exploiting the passenger ACO1-deficiency arising from 9p21 deletions to kill T-cell lymphoblastic neoplasia cells.

    abstract::Precursor T-cell lymphoblastic neoplasms are aggressive malignancies in need for more effective and specific therapeutic treatments. A significant fraction of these neoplasms harbor deletions on the locus 9p21, targeting the tumor suppressor CDKN2A but also deleting the aconitase 1 (ACO1) gene, a neighboring housekeep...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgz185

    authors: Gonzalez-Sanchez L,Cobos-Fernandez MA,Lopez-Nieva P,Villa-Morales M,Stamatakis K,Cuezva JM,Marin-Rubio JL,Vazquez-Dominguez I,Gonzalez-Vasconcellos I,Salido E,Llamas P,Lopez-Lorenzo JL,Santos J,Fernandez-Piqueras J

    更新日期:2020-08-12 00:00:00

  • Inactivating mutations of the human base excision repair gene NEIL1 in gastric cancer.

    abstract::Oxidized DNA base lesions, such as thymine glycol (Tg) and 8-hydroxyguanine, are often toxic and mutagenic and have been implicated in carcinogenesis. To clarify whether NEIL1 protein, which exhibits excision repair activity towards such base lesions, is involved in gastric carcinogenesis, we examined 71 primary gastr...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgh267

    authors: Shinmura K,Tao H,Goto M,Igarashi H,Taniguchi T,Maekawa M,Takezaki T,Sugimura H

    更新日期:2004-12-01 00:00:00

  • Modulation of the PD-1/PD-L1 immune checkpoint axis during inflammation-associated lung tumorigenesis.

    abstract::Chronic obstructive pulmonary disease (COPD) is a significant risk factor for lung cancer. One potential mechanism through which COPD contributes to lung cancer development could be through generation of an immunosuppressive microenvironment that allows tumor formation and progression. In this study, we compared the s...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgaa059

    authors: Narayanapillai SC,Han YH,Song JM,Kebede ME,Upadhyaya P,Kassie F

    更新日期:2020-11-13 00:00:00

  • Effect of heterocyclic amines and beef extract on chromosome aberrations and sister chromatid exchanges in cultured human lymphocytes.

    abstract::Two of the major bacterial mutagens formed in heated meat products, 2-amino-3-methylimidazo[4,5-f]quinoline and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline or the basic fraction of beef extract induced a low frequency of sister chromatid exchanges in human lymphocyte cultures in the presence of metabolic activation....

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/10.3.429

    authors: Aeschbacher HU,Ruch E

    更新日期:1989-03-01 00:00:00

  • Restoration of preferential and strand specific gene repair in group 2 Chinese hamster ovary mutants (UV5) by the XPD (ERCC2) gene.

    abstract::It has recently been reported that the XPD (ERCC2) gene is an integral component of the basal transcription factor TFIIH. We have studied the direct role of this repair gene on the fine structure of DNA repair in hamster cells. The gene and strand specific DNA repair of UV induced pyrimidine dimers was determined in w...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/18.4.681

    authors: Cullinane C,Weber CA,Dianov G,Bohr VA

    更新日期:1997-04-01 00:00:00

  • Ethoxyquin alone induces preneoplastic changes in rat kidney whilst preventing induction of such lesions in liver by aflatoxin B1.

    abstract::Pretreatment of Fischer 344 rats with the antioxidant ethoxyquin (EQ), followed by administration of aflatoxin B1 (AFB1) in the continuing presence of EQ was used to examine the effect of the antioxidant on liver and kidney. EQ (0.5% in diet) completely prevented the formation of AFB1-induced preneoplastic liver lesio...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/8.5.723

    authors: Manson MM,Green JA,Driver HE

    更新日期:1987-05-01 00:00:00