The ATM tumour suppressor gene is down-regulated in EBV-associated nasopharyngeal carcinoma

被引：82

作者：

Bose, Shikha ^{[1
]}

Yap, Lee-Fah ^{[2
]}

Fung, Matthew ^{[1
]}

Starzcynski, Jane ^{[5
]}

Saleh, Amyza ^{[2
]}

Morgan, Susan ^{[1
]}

Dawson, Christopher ^{[1
]}

Chukwuma, Marilyn B. ^{[1
]}

Maina, Esther ^{[1
]}

Buettner, Maike ^{[4
]}

Wei, Wenbin ^{[1
]}

Arrand, John ^{[1
]}

Lim, Paul V. H. ^{[3
]}

Young, Lawrence S. ^{[1
]}

Teo, Soo Hwang ^{[2
]}

Stankovic, Tatjana ^{[1
]}

Woodman, Claran B. J. ^{[1
]}

Murray, Paul G. ^{[1
]}

机构：

[1] Univ Birmingham, CRUK Inst Canc Studies, Sch Med, Birmingham B15 2TT, W Midlands, England

[2] Subang Jaya Med Ctr, Floor Outpatient Ctr 2, Canc Res Initiat Fdn, Subang Jaya 47500, Selangor, Malaysia

[3] Tung Shin Hosp, Kuala Lumpur, Malaysia

[4] Univ Erlangen Nurnberg, Inst Pathol, D-91054 Erlangen, Germany

[5] Birmingham Heartlands Hosp, Birmingham B9 5SS, W Midlands, England

来源：

JOURNAL OF PATHOLOGY | 2009年 / 217卷 / 03期

关键词：

nasopharyngeal carcinoma; ATM; Epstein-Barr virus; EPSTEIN-BARR-VIRUS; CHRONIC LYMPHOCYTIC-LEUKEMIA; MUTATION STATUS; FREE SURVIVAL; DNA-DAMAGE; EXPRESSION; CELLS; LYMPHOMA; PHOSPHORYLATION; PROTEIN;

D O I：

10.1002/path.2487

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. Copyright (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

引用

页码：345 / 352

页数：8

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