Heterogeneous methylation of the O(6)-methylguanine-DNA methyltransferase promoter in immortalized IMR90 cell lines.

Abstract:

:Transcriptional silencing of the DNA repair protein, O6-methylguanine-DNA methyltransferase (MGMT), occurs only in malignant or transformed cell lines, and such MGMT-deficient cells are hypersensitive to chemotherapeutic alkylating agents such as 1, 3-bis (2-chloroethyl)-1-nitrosourea (BCNU) and temozolomide. Previously we demonstrated in a panel of established cell lines that the lack of gene expression correlated with methylation within the CpG island in the MGMT 5' gene flank. Now, we investigated the relationship between CpG methylation, MGMT suppression and drug-sensitivity in normal, diploid MGMT-expressing IMR90 cells and five immortalized sublines (AA, EE, J, KK and Pool), four of which have silenced MGMT. As expected, the MGMT-expressing parental cells were most drug-resistant and free of promoter methylation, whereas the MGMT-silenced immortal sublines were more drug-sensitive and promoter-methylated. Surprisingly, the sole MGMT-positive immortal subline, (AA) showed some promoter methylation although it was relatively drug-resistant; and an apparently MGMT-negative subline, (EE) showed unexpectedly low levels of methylation. We determined if these discrepancies were due to heterogeneity (cellular or allelic) and if this reflected transitional states between expressing and silenced phenotypes. Analysis of the methylation status of CpGs by genomic sequencing of cloned single copy DNA confirmed heterogeneity in both these sublines. With increasing cell culture passage, CpG methylation progressively increased with a concomitant trend to a completely MGMT-silenced phenotype in these sublines.

journal_name

Int J Oncol

authors

Danam RP,Howell SR,Remack JS,Brent TP

doi

10.3892/ijo.18.6.1187

keywords:

subject

Has Abstract

pub_date

2001-06-01 00:00:00

pages

1187-93

issue

6

eissn

1019-6439

issn

1791-2423

journal_volume

18

pub_type

杂志文章
  • Allelic imbalance and microsatellite instability in plasma DNA released from polyclonal pancreatic adenocarcinoma.

    abstract::Evidence of circulating soluble DNA in blood-stream of cancer patients has emerged. Because the plasma DNA is largely derived from cancer cells, genetic analysis of plasma DNA is important to understand the molecular events occurred in cancer patient. Seven microsatellite markers in the soluble plasma DNA from patient...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.21.5.949

    authors: Moriyama H,Matsubara N,Kanbara T,Mori M,Matsuoka J,Yoshino T,Takakura N,Shimizu K,Takaka N

    更新日期:2002-11-01 00:00:00

  • Effects related to indomethacin prolonged survival and decreased tumor-growth in a mouse-tumor model with cytokine dependent cancer cachexia.

    abstract::Tumor-bearing mice with two different locally growing malignant tumors (epithelial like, MCG 101; malignant melanoma, K1735-M2) were used to evaluate the putative role of prostaglandins for survival and local tumor growth in experimental cancer. Daily systemic injections of indomethacin (1 mu g/g bw) were used to bloc...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.7.6.1405

    authors: Lonnroth C,Svaninger G,Gelin J,Cahlin C,Iresjo B,Cvetkovska E,Edstrom S,Andersson M,Svanberg E,Lundholm K

    更新日期:1995-12-01 00:00:00

  • Anticancer potential of novel curcumin analogs towards castrate-resistant prostate cancer.

    abstract::Prostate cancer is initially sensitive to hormone therapy; however, over time the majority of patients progress to a hormone-insensitive form classified as castration-resistant prostate cancer (CRPC). CRPC is highly metastatic and patients have a poor prognosis. Thus, new drugs for the treatment of this disease are re...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2017.4207

    authors: Chen S,Nimick M,Cridge AG,Hawkins BC,Rosengren RJ

    更新日期:2018-02-01 00:00:00

  • Identification of circulating prostate cancer cells: a challenge to the clinical implementation of molecular biology (review).

    abstract::Conventional diagnosis of prostate cancer does not appear to be sensitive enough to differentiate pre-operatively between organ-confined and extracapsular disease. New technologies, arising from the field of molecular biology, have been introduced to improve diagnosis and their implementation into the clinical practic...

    journal_title:International journal of oncology

    pub_type: 杂志文章,评审

    doi:

    authors: Schamhart DH,Maiazza R,Kurth KH

    更新日期:2005-03-01 00:00:00

  • Icariin induces apoptosis in mouse MLTC-10 Leydig tumor cells through activation of the mitochondrial pathway and down-regulation of the expression of piwil4.

    abstract::The Leydig cell tumor, derived from interstitial cells, is a rare neoplasm. In most cases, Leydig cell tumors are benign, however, if the tumor is malignant, no effective treatments are currently available. In this study, we aimed to evaluate the effects of icariin on the growth of the mouse Leydig tumor cell line MLT...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2011.1086

    authors: Wang Q,Hao J,Pu J,Zhao L,Lü Z,Hu J,Yu Q,Wang Y,Xie Y,Li G

    更新日期:2011-10-01 00:00:00

  • Sphere-forming stem-like cell populations with drug resistance in human sarcoma cell lines.

    abstract::The presence of cancer stem cells in both solid and hematopoietic malignancies, has been recently linked to their pathogenesis. Sarcomas are rare, and diversely characterized by degrees of mesenchymal differentiation. The aim of the current study was to demonstrate whether the human sarcoma cell lines, osteosarcoma MG...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Fujii H,Honoki K,Tsujiuchi T,Kido A,Yoshitani K,Takakura Y

    更新日期:2009-05-01 00:00:00

  • VEGF in nuclear medicine: Clinical application in cancer and future perspectives (Review).

    abstract::Clinical trials using antiangiogenic drugs revealed their potential against cancer. Unfortunately, a large percentage of patients does not yet benefit from this therapeutic approach highlighting the need of diagnostic tools to non-invasively evaluate and monitor response to therapy. It would also allow to predict whic...

    journal_title:International journal of oncology

    pub_type: 杂志文章,评审

    doi:10.3892/ijo.2016.3553

    authors: Taurone S,Galli F,Signore A,Agostinelli E,Dierckx RA,Minni A,Pucci M,Artico M

    更新日期:2016-08-01 00:00:00

  • Comparative integromics on VEGF family members.

    abstract::VEGF, Hedgehog, FGF, Notch, and WNT signaling pathways network together for vascular remodeling during embryogenesis, tissue regeneration, and carcinogenesis. VEGFA (VEGF), VEGFB, VEGFC, VEGFD (FIGF) and PGF (PlGF) are VEGF family ligands for receptor tyrosine kinases, including VEGFR1 (FLT1), VEGFR2 (KDR) and VEGFR3 ...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Katoh Y,Katoh M

    更新日期:2006-06-01 00:00:00

  • Leptin receptor expression and cell signaling in breast cancer.

    abstract::Obesity is considered a risk factor for many cancers, including breast cancer. Our laboratory has previously shown that leptin is mitogenic in many cancer cell lines, including breast. Information regarding the effects of high leptin levels on leptin receptor expression and signaling is lacking. The purpose of this st...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Frankenberry KA,Skinner H,Somasundar P,McFadden DW,Vona-Davis LC

    更新日期:2006-04-01 00:00:00

  • Organophosphorous pesticides and estrogen induce transformation of breast cells affecting p53 and c-Ha-ras genes.

    abstract::Cancer progression has been associated with an increase in genomic instability indicated by inactivation of tumor suppressor genes and activation of oncogenes. Epidemiological and experimental evidence has implicated estrogens in the etiology of breast cancer. To study environmental organophosphorous pesticides is of ...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo_00000421

    authors: Calaf GM,Echiburu-Chau C,Roy D

    更新日期:2009-11-01 00:00:00

  • Kinase inhibitor screening identifies CDK4 as a potential therapeutic target for melanoma.

    abstract::Despite recent advances in targeted therapies and immunotherapies metastatic melanoma remains only rarely curable. The objective of the present study was to identify novel therapeutic targets for metastatic melanoma. A library of 160 well-characterised and potent protein kinase inhibitors was screened in the BRAF muta...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2015.3097

    authors: Mahgoub T,Eustace AJ,Collins DM,Walsh N,O'Donovan N,Crown J

    更新日期:2015-09-01 00:00:00

  • Prognostic impact of disseminated tumor cells and microRNA-17-92 cluster deregulation in gastrointestinal cancer.

    abstract::The presence of tumor cells in the bone marrow (BM) could be relevant to identifying high risk of disease progression and death in gastrointestinal cancer. However, the molecular profile associated with disseminated tumor cells (DTCs) homing to the BM has yet to be defined. MicroRNAs (miRNA) play key roles in cellular...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2011.1112

    authors: Valladares-Ayerbes M,Blanco M,Haz M,Medina V,Iglesias-Díaz P,Lorenzo-Patiño MJ,Reboredo M,Santamarina I,Figueroa A,Antón-Aparicio LM,Calvo L

    更新日期:2011-11-01 00:00:00

  • [Corrigendum] Overexpression of lncRNA EGFR‑AS1 is associated with a poor prognosis and promotes chemotherapy resistance in non‑small cell lung cancer.

    abstract::After the publication of the article, the authors have realized that the affiliation presented for the joint co‑author listed on the paper (Jian‑Ren Tu) was incorrect. The correct author list (and affiliations) should therefore have been published as follows: Yu‑Hua Xu1*, Jian‑Ren Tu2*, Tian‑Tian Zhao3, Shi‑Guang Xie3...

    journal_title:International journal of oncology

    pub_type: 杂志文章,已发布勘误

    doi:10.3892/ijo.2019.4686

    authors: Xu YH,Tu JR,Zhao TT,Xie SG,Tang SB

    更新日期:2019-07-01 00:00:00

  • Episome generated C-myc antisense RNA inhibits growth and tumorigenicity of a human neuroendocrine tumor-cell line.

    abstract::The neuroepithelioma cell line CHP100 expresses low but detectable amounts of N-myc protein together with large amounts of c-myc protein. We have recently demonstrated that antisense inhibition of N-myc expression in CHP100 cells leads to decreased in vitro growth and alterations in cellular morphology without affecti...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.6.1.175

    authors: Rosolen A,Frascella E,Toretsky J,Neckers L

    更新日期:1995-01-01 00:00:00

  • Differences in loss of p16INK4 protein expression by promoter methylation between left- and right-sided primary colorectal carcinomas.

    abstract::The p16INK4 gene, encoding a cyclin-dependent kinase inhibitor, is frequently methylated in colorectal cancer, and a side-specific methylation frequency was suggested. To clarify the frequency of real loss of tumor suppressor function dependent on anatomical localization, we investigated 43 primary colorectal carcinom...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Schneider-Stock R,Boltze C,Peters B,Höpfner T,Meyer F,Lippert H,Roessner A

    更新日期:2003-10-01 00:00:00

  • Involvement of P-glycoprotein in an in vitro blood-brain barrier model.

    abstract::The P-glycoprotein (P-gp) multidrug transporter is present at the luminal face of the brain capillary endothelial cells that contribute to the blood-brain barrier. To study its role in transendothelial anticancer drug transport, we made use of a co-culture system formed of bovine brain capillary endothelial cells and ...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Joly B,Lecureur V,Puozzo C,Guillouzo A,Fardel O

    更新日期:1996-11-01 00:00:00

  • Chemosensitization of oral squamous cell carcinoma cells to cisplatin by histone deacetylase inhibitor, suberoylanilide hydroxamic acid.

    abstract::In the present study, the precise mechanism of the enhancing action of histone deacetylase (HDAC) inhibitors on cisplatin (CDDP)-induced apoptosis was investigated using suberoylanilide hydroxamic acid (SAHA) in human oral squamous cell carcinoma cells (HSC-3). HDAC inhibitors are promising novel compounds for the tre...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Rikiishi H,Shinohara F,Sato T,Sato Y,Suzuki M,Echigo S

    更新日期:2007-05-01 00:00:00

  • Old and new insights into the mechanisms of action of two nucleoside analogs active in lymphoid malignancies: fludarabine and cladribine (review).

    abstract::This review focuses on two chemotherapeutic agents belonging to the family of purine analogs, 9-beta-D-arabinosyl-2-fluoroadenine-5'-monophosphate (F-ara-AMP, fludarabine), which is the soluble form of F-ara-A, and 2-chloro-2'-deoxyadenosine (CdA, cladribine). Both compounds display remarkable activity in malignancies...

    journal_title:International journal of oncology

    pub_type: 杂志文章,评审

    doi:

    authors: Van den Neste E,Cardoen S,Offner F,Bontemps F

    更新日期:2005-10-01 00:00:00

  • Interleukin-2 and 13-cis retinoic acid in the treatment of minimal residual disease: a phase II study.

    abstract::Interleukin-2 (IL-2) which has no cross-resistance with chemotherapy, has given responses in tumors resistant to chemotherapy, and shown to be more effective when tumor burden is low. 13-cis retinoic acid (RA) has immunomodulatory properties, potentially synergistic with IL-2. The objective of this pilot phase II stud...

    journal_title:International journal of oncology

    pub_type: 临床试验,杂志文章

    doi:

    authors: Recchia F,De Filippis S,Rosselli M,Saggio G,Fumagalli L,Rea S

    更新日期:2002-06-01 00:00:00

  • Overexpression of RII beta regulatory subunit of protein kinase A induces growth inhibition and reverse-transformation in SK-N-SH human neuroblastoma cells.

    abstract::SK-N-SH human neuroblastoma cell line was employed to test whether direct introduction of the RII beta subunit of PKA could induce growth inhibition and reverse-transformation of cancer cells. We infected SK-N-SH cells with an RII beta expression construct and the clonal line with the highest expression level was sele...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.8.4.663

    authors: Kim S,Lee G,Chochung Y,Park S,Hong S

    更新日期:1996-04-01 00:00:00

  • Comparative genomics on mammalian Fgf3-Fgf4 locus.

    abstract::The CCND1-ORAOV1-FGF19-FGF4-FGF3-TMEM16A-FADD-PPFIA1-CTTN (EMS1) locus at human chromosome 11q13.3 is amplified in head and neck tumors, esophageal cancer, Kaposi's sarcoma, bladder tumors, breast cancer, and liver cancer. Fgf4 mRNA is expressed in embryonic stem (ES) cells depending on Sox2 and Pou5f1 (Oct3/Oct4) tra...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Katoh M,Katoh M

    更新日期:2005-07-01 00:00:00

  • Antiproliferative effect of chlorophyllin derived from a traditional Chinese medicine Bombyx mori excreta on human breast cancer MCF-7 cells.

    abstract::Chlorophyllin (CHL) is the sodium-copper salts of chlorophyll derivatives. In this study, the CHL was derived from a traditional Chinese medicine, the Bombyx mori excreta. The CHL, at concentrations 25-400 microg/ml, reduced the proliferation of HL-60, K-562, S-180, and MCF-7 cells by 8.2-95.7% after 72 h of incubatio...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Chiu LC,Kong CK,Ooi VE

    更新日期:2003-09-01 00:00:00

  • Substrate stiffness affects epithelial-mesenchymal transition of cervical cancer cells through miR-106b and its target protein DAB2.

    abstract::The effects of different substrate stiffness were investigated on epithelial-mesenchymal transition (EMT) of cervical cancer cell lines and the role of miR-106b and its target protein DAB2 therein. Cervical cancer cell lines HeLa and SiHa were cultured on artificial substrates with different stiffness prepared using d...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2017.3978

    authors: Piao J,You K,Guo Y,Zhang Y,Li Z,Geng L

    更新日期:2017-06-01 00:00:00

  • GSH loss per se does not affect neuroblastoma survival and is not genotoxic.

    abstract::Depletion of glutathione (GSH) by buthionine sulfoximine (BSO) has been reported to be toxic against some cancer cells and to sensitize many tumours including neuroblastoma (NB) to anticancer drugs. The balance between the production rate of reactive oxygen species (ROS) and the function of GSH affects the intracellul...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Marengo B,Balbis E,Patriarca S,De Ciucis C,Furfaro A,Nitti M,Marinari UM,Pronzato MA,Traverso N,Domenicotti C

    更新日期:2008-01-01 00:00:00

  • P53 and its implication in apoptosis (review).

    abstract::The tumor suppressor protein p53 is one of the most important manipulators of the cell cycle. By interaction with targets such as WAF1/CIP1, mdm2 or GADD45 p53 functions as a negative or positive regulator of the cell cycle. After DNA damage p53 is implicated in growth arrest of cells in the G(1) phase of the cell cyc...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.6.5.1129

    authors: Gotz C,Montenarh M

    更新日期:1995-05-01 00:00:00

  • Hypoxia switches glucose depletion-induced necrosis to phosphoinositide 3-kinase/Akt-dependent apoptosis in A549 lung adenocarcinoma cells.

    abstract::In solid tumours, necrosis is commonly found in the core region in response to metabolic stress that results from oxygen and glucose depletion (OGD) due to insufficient vascularization and has been implicated in tumour progression. We have previously shown that metabolic stress due to glucose depletion (GD) induces ne...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Kim CH,Ko AR,Lee SY,Jeon HM,Kim SM,Park HG,Han SI,Kang HS

    更新日期:2010-01-01 00:00:00

  • The uptake of a monoclonal antibody (Po66) in lung tumour cell aggregates involves a phagocytose-like phenomenon.

    abstract::The efficacy of radioimmunotherapy with radiolabelled monoclonal antibody (Mab) depends on the amount of antibody taken up by the tumour and on its intratumoral distribution. Multicellular spheroids (MTS) of lung cell carcinoma was investigated to study cellular and subcellular distribution of a Mab Po66 labelled with...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.10.3.609

    authors: Dazord L,Thomas D,Brichory F,Cavalier A,Meritte H,Desrues B,Cauletmaugendre S,Bourguet P

    更新日期:1997-03-01 00:00:00

  • Expression of Müllerian inhibiting substance type II receptor and antiproliferative effects of MIS on human cervical cancer.

    abstract::This study aimed to analyze expression of Müllerian inhibiting substance type II receptor (MISRII) protein and mRNA in cervical neoplasia, to demonstrate the growth inhibition of cervical cancer cells by administration of highly purified recombinant human Müllerian inhibiting substa...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2012.1370

    authors: Song JY,Jo HH,Kim MR,Lew YO,Ryu KS,Cha JH,Kang CS,Donahoe PK,MacLaughlin DT,Kim JH

    更新日期:2012-06-01 00:00:00

  • Utility of transrectal ultrasonography guidance and seven key elements of operative skill for early recovery of urinary continence after laparoscopic radical prostatectomy.

    abstract::In the present study, we report the utility of transrectal ultrasonography guidance for laparoscopic radical prostatectomy (LRP), and the effect of a novel surgical approach of 'seven key elements of operative skill for the early recovery of urinary continence' ('7 key elements'). Among 170 patients who underwent lapa...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2010.865

    authors: Azuma H,Ibuki N,Inamoto T,Koyama K,Utimoto S,Fujisue Y,Mizutani Y,Nomi H,Ubai T,Katsuoka Y

    更新日期:2011-02-01 00:00:00

  • Establishment of human fibroma cell lines from a MEN1 patient by introduction of either hTERT or SV40 early region.

    abstract::Establishment of tumor cell lines as model systems for studying tumor biology or as a part of immunotherapeutic anti-cancer strategies is of high importance, whereby the highest possible preservation of the original tumor cell phenotype is a prerequisite for these aims. Since overexpression of the catalytic subunit of...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.26.4.961

    authors: Voglauer R,Grillari J,Fortschegger K,Wieser M,Sterovsky T,Gunsberg P,Katinger H,Pfragner R

    更新日期:2005-04-01 00:00:00