Methylation of the ATM promoter in glioma cells alters ionizing radiation sensitivity.

Biochemical and Biophysical Research Communications
Kanaklata RoyBrendan D Price

Abstract

Glioblastomas are among the malignancies most resistant to radiation therapy. In contrast, cells lacking the ATM protein are highly sensitive to ionizing radiation. The relationship between ATM protein expression and radiosensitivity in 3 glioma cell lines was examined. T98G cells exhibited normal levels of ATM protein, whereas U118 and U87 cells had significantly lower levels of ATM and increased (>2-fold) sensitivity to ionizing radiation compared to T98G cells. The ATM promoter was methylated in U87 cells. Demethylation by azacytidine treatment increased ATM protein levels in the U87 cells and decreased their radiosensitivity. In contrast, the ATM promoter in U118 cells was not methylated. Further, expression of exogenous ATM did not significantly alter the radiosensitivity of U118 cells. ATM expression is therefore heterogeneous in the glioma cells examined. In conclusion, methylation of the ATM promoter may account for the variable radiosensitivity and heterogeneous ATM expression in a fraction of glioma cells.

References

Jan 1, 1981·Differentiation; Research in Biological Diversity·M OsbornK Bayreuther
Jan 1, 1995·Cytogenetics and Cell Genetics·T K PanditaC R Geard
Sep 3, 1996·Proceedings of the National Academy of Sciences of the United States of America·J G HermanS B Baylin
Sep 2, 1998·Trends in Genetics : TIG·P A JeggoA R Lehmann
Jan 19, 2000·Proceedings of the National Academy of Sciences of the United States of America·M J ChongP J McKinnon
Apr 6, 2000·Journal of the National Cancer Institute·M EstellerJ G Herman
May 31, 2001·International Journal of Radiation Oncology, Biology, Physics·S TribiusD Casper
Jun 29, 2001·Journal of Clinical Pathology·J Boultwood
Jan 24, 2002·Proceedings of the National Academy of Sciences of the United States of America·Shaun P ScottMartin F Lavin
Jan 31, 2003·Nature·Christopher J Bakkenist, Michael B Kastan
Mar 4, 2003·Nature Reviews. Cancer·Yosef Shiloh
Apr 4, 2003·Human Mutation·Jonine L BernsteinUNKNOWN WECARE Study Collaborative Group
Nov 25, 2003·Leukemia·F Gumy-PauseA-P Sappino
Jan 28, 2004·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Lingbao AiChun-Yang Fan
Apr 20, 2004·Biochemical and Biophysical Research Communications·Shujuan ChenBrendan D Price
Dec 18, 2004·Mutation Research·Martin F LavinNuri Gueven
Sep 6, 2005·Proceedings of the National Academy of Sciences of the United States of America·Yingli SunBrendan D Price
Sep 29, 2005·Journal of Clinical Pathology·A M R Taylor, P J Byrd
Dec 13, 2005·Nature Clinical Practice. Oncology·Stephen B Baylin

❮ Previous
Next ❯

Citations

Jan 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Hailiang HuRichard A Gatti
Aug 25, 2012·Cancer Biotherapy & Radiopharmaceuticals·Li WangJuLun Yang
Jan 1, 2009·Journal of Bronchology & Interventional Pulmonology·Takahiro NakajimaIchiro Yoshino
May 23, 2013·PLoS Genetics·Nathan T MartinHailiang Hu
Aug 18, 2010·Human Cell·Romaica A Omaruddin, M Ahmad Chaudhry
Dec 30, 2011·Leukemia & Lymphoma·Thomas MikeskaAlexander Dobrovic
Jun 16, 2010·International Journal of Radiation Biology·Shumei MaXiaodong Liu
Dec 17, 2014·Pharmacology & Therapeutics·Anika Maria Weber, Anderson Joseph Ryan
Feb 14, 2009·International Journal of Radiation Oncology, Biology, Physics·Harlinde De SchutterSandra Nuyts
Feb 11, 2012·International Journal of Cancer. Journal International Du Cancer·Frank RoossinkMarcel A T M van Vugt
Oct 26, 2012·The Journal of Pathology·Andrew D BeggsIan P M Tomlinson
May 12, 2015·Epigenetics : Official Journal of the DNA Methylation Society·Xiaofei ChenCristina M Furdui
Jan 8, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Aleksandra Majchrzak-CelińskaWanda Baer-Dubowska
May 28, 2014·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Kim M SmitsPhilippe Lambin
Dec 3, 2016·Nucleic Acids Research·Yibin LiuG Mike Makrigiorgos
Oct 17, 2017·Expert Review of Clinical Immunology·Majid Zaki-DizajiAsghar Aghamohammadi
Mar 15, 2019·Molecular Human Reproduction·Tomoko HirakawaHisashi Narahara
Jun 17, 2009·Journal of Medical Imaging and Radiation Oncology·Z M FangR A Clarke
Jun 4, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yutaka SuehiroYuji Hinoda
Oct 18, 2020·Translational Oncology·Emma McCannSimone Marcone

❮ Previous
Next ❯

Related Concepts

Related Feeds

Ataxia telangiectasia

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.

Ataxia telangiectasia (MDS)

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.