The ATM tumour suppressor gene is down-regulated in EBV-associated nasopharyngeal carcinoma.
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.
Bose
Shikha
S
Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham B15 2TT, UK.
Yap
Lee-Fah
LF
Fung
Matthew
M
Starzcynski
Jane
J
Saleh
Amyza
A
Morgan
Susan
S
Dawson
Christopher
C
Chukwuma
Marilyn B
MB
Maina
Esther
E
Buettner
Maike
M
Wei
Wenbin
W
Arrand
John
J
Lim
Paul V H
PV
Young
Lawrence S
LS
Teo
Soo Hwang
SH
Stankovic
Tatjana
T
Woodman
Ciaran B J
CB
Murray
Paul G
PG
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
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