Identification of aberrantly methylated genes in association with adult T-cell leukemia

Cancer Research
Jun-Ichirou YasunagaM Matsuoka

Abstract

In this study, we identified 53 aberrantly hypermethylated DNA sequences in adult T-cell leukemia (ATL) cells using methylated CpG island amplification/representational difference analysis method. We also observed a proportionate increase in the methylation density of these regions with disease progression. Seven genes, which were expressed in normal T cells, but suppressed in ATL cells, were identified near the hypermethylated regions. Among these silenced genes, Kruppel-like factor 4 (KLF4) gene is a cell cycle regulator and early growth response 3 (EGR3) gene is a critical transcriptional factor for induction of Fas ligand (FasL) expression. Treatment with 5-aza-2'-deoxycytidine resulted in the recovery of their transcription, indicating that their silencing might be associated with DNA hypermethylation. To study their functions in ATL cells, we transfected recombinant adenovirus vectors expressing KLF4 and EGR3 genes. Expression of KLF4 induced apoptosis of ATL cells whereas enforced expression of EGR3 induced the expression of FasL gene, resulting in apoptosis. Thus, suppressed expression of EGR3 enabled ATL cells to escape from activation-induced cell death mediated by FasL. Our results showed that the methylated CpG isla...Continue Reading

References

Oct 3, 1985·Nature·F Wong-Staal, R C Gallo
Dec 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·B J PoieszR C Gallo
Aug 11, 1994·Nucleic Acids Research·S J ClarkM Frommer
Apr 1, 1993·Electrophoresis·Y HayashizakiS Wada
Mar 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·T UshijimaM Nagao
Jun 15, 1997·Nucleic Acids Research·Z Xiong, P W Laird
Jun 25, 1998·Molecular and Cellular Biology·P R Mittelstadt, J D Ashwell
Feb 1, 2000·International Journal of Cancer. Journal International Du Cancer·K ArisawaS Shirahama
Oct 26, 2000·Nature·P H Krammer
Mar 13, 2001·Annual Review of Immunology·M Yoshida
Mar 14, 2002·Proceedings of the National Academy of Sciences of the United States of America·Daiya Takai, Peter A Jones
Nov 13, 2002·The Journal of Biological Chemistry·Hong S YoonVincent W Yang
Oct 31, 2003·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Jean-Pierre Issa
Nov 25, 2003·The Journal of Biological Chemistry·Hong S Yoon, Vincent W Yang
Nov 25, 2003·The EMBO Journal·Esteban BallestarManel Esteller
Dec 23, 2003·International Journal of Hematology·Genoveffa FranchiniJake R Fullen
Dec 23, 2003·International Journal of Hematology·Charles R M Bangham
Mar 3, 2004·International Journal of Cancer. Journal International Du Cancer·Satoshi TakedaMasao Matsuoka

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Citations

Nov 30, 2006·Immunology and Cell Biology·A E Germenis, V Karanikas
Jan 16, 2010·The Journal of Biological Chemistry·Yanyan TianZhihua Liu
Apr 1, 2008·International Immunology·Isharat YusufDavid A Fruman
Aug 12, 2005·Current Opinion in Oncology·Lee Ratner
Aug 12, 2010·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Nilesh V PatelVincent W Yang
Jul 23, 2008·Molecular Cancer Therapeutics·Sung Dae ChoStephen Safe
Mar 4, 2008·Molecular Cancer Research : MCR·Shuang LiuYan Dong
Sep 7, 2006·Blood·Michael G KharasDavid A Fruman
Feb 7, 2007·Cell Stress & Chaperones·Ying LiuXianzhong Xiao
Sep 19, 2007·International Journal of Hematology·Yorifumi Satou, Masao Matsuoka
Dec 1, 2009·Epigenomics·Minoru ToyotaYasuhisa Shinomura
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Kazuo YamadaTakeo Yoshikawa
Jul 25, 2009·The Journal of Investigative Dermatology·Kazuhiro KawaiTakuro Kanekura
Apr 12, 2005·Cancer Science·Toshikazu Ushijima, Eriko Okochi-Takada
Aug 9, 2008·International Journal of Cancer. Journal International Du Cancer·Ayuko TaniguchiMasanori Daibata
Apr 23, 2013·Reviews in Medical Virology·Yorifumi Satou, Masao Matsuoka
Apr 2, 2011·International Journal of Cancer. Journal International Du Cancer·María J Ruiz-MagañaCarmen Ruiz-Ruiz
Feb 19, 2014·British Journal of Haematology·Jorge J CastilloEmmanuel Apor
Jan 18, 2006·Experimental Hematology·Rasheed KhanEva Hellström-Lindberg

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