title: The ATM tumour suppressor gene is down-regulated in EBV-associated nasopharyngeal carcinoma.
abstract: A micro-array analysis using biopsies from patients with EBV-positive undifferentiated nasopharyngeal carcinoma (NPC) and from cancer-free controls revealed down-regulation of tumour suppressor genes (TSG) not previously associated with this disease; one such gene was the ataxia telangiectasia mutated (ATM) gene. Q-PCR confirmed down-regulation of ATM mRNA and ATM protein expression in tumour cells was weak or absent in almost all cases. In NPC cell lines, however, ATM was down-regulated only in the EBV-positive line, C666.1, and in none of five EBV-negative lines. In vitro infection of EBV-negative NPC cell lines with a recombinant EBV was followed by the down-regulation of ATM mRNA and protein, and only EBV-positive cells showed a defective DNA damage response following gamma-irradiation. Our data suggest that loss of ATM function could be an important step in the pathogenesis of NPC, and may have implications for the treatment of this disease.
authors.affiliation: Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Shikha
authors.initials: S
authors.lastname: Bose
authors.forename: Lee-Fah
authors.initials: LF
authors.lastname: Yap
authors.forename: Matthew
authors.initials: M
authors.lastname: Fung
authors.forename: Jane
authors.initials: J
authors.lastname: Starzcynski
authors.forename: Amyza
authors.initials: A
authors.lastname: Saleh
authors.forename: Susan
authors.initials: S
authors.lastname: Morgan
authors.forename: Christopher
authors.initials: C
authors.lastname: Dawson
authors.forename: Marilyn B
authors.initials: MB
authors.lastname: Chukwuma
authors.forename: Esther
authors.initials: E
authors.lastname: Maina
authors.forename: Maike
authors.initials: M
authors.lastname: Buettner
authors.forename: Wenbin
authors.initials: W
authors.lastname: Wei
authors.forename: John
authors.initials: J
authors.lastname: Arrand
authors.forename: Paul V H
authors.initials: PV
authors.lastname: Lim
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Young
authors.forename: Soo Hwang
authors.initials: SH
authors.lastname: Teo
authors.forename: Tatjana
authors.initials: T
authors.lastname: Stankovic
authors.forename: Ciaran B J
authors.initials: CB
authors.lastname: Woodman
authors.forename: Paul G
authors.initials: PG
authors.lastname: Murray
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000821:virology; D064007:Ataxia Telangiectasia Mutated Proteins; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000032:analysis / Q000235:genetics*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D015536:Down-Regulation; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human; D006801:Humans; D007150:Immunohistochemistry; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000821:virology; D020411:Oligonucleotide Array Sequence Analysis; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000235:genetics*; D014412:Tumor Virus Infections / Q000150:complications / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases