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

Shikha Bose; Lee Fah Yap; Matthew Fung; Jane Starzcynski; Amyza Saleh; Susan Morgan; Christopher Dawson; Marilyn B. Chukwuma; Esther Maina; Maike Buettner; Wenbin Wei; John Arrand; Paul V.H. Lim; Lawrence S. Young; Soo Hwang Teo; Tatjana Stankovic; Ciaran B.J. Woodman; Paul G. Murray

doi:10.1002/path.2487

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

Shikha Bose, Lee Fah Yap, Matthew Fung, Jane Starzcynski, Amyza Saleh, Susan Morgan, Christopher Dawson, Marilyn B. Chukwuma, Esther Maina, Maike Buettner, Wenbin Wei, John Arrand, Paul V.H. Lim, Lawrence S. Young, Soo Hwang Teo, Tatjana Stankovic, Ciaran B.J. Woodman, Paul G. Murray

Research output: Contribution to journal › Article › peer-review

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 γ-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.

Original language	English
Pages (from-to)	345-352
Number of pages	8
Journal	The Journal of Pathology
Volume	217
Issue number	3
DOIs	https://doi.org/10.1002/path.2487
Publication status	Published - Feb 2009
Externally published	Yes

Keywords

ATM
Epstein-Barr virus
Nasopharyngeal carcinoma

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/path.2487

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Bose, S., Yap, L. F., Fung, M., Starzcynski, J., Saleh, A., Morgan, S., Dawson, C., Chukwuma, M. B., Maina, E., Buettner, M., Wei, W., Arrand, J., Lim, P. V. H., Young, L. S., Teo, S. H., Stankovic, T., Woodman, C. B. J., & Murray, P. G. (2009). The ATM tumour suppressor gene is down-regulated in EBV-associated nasopharyngeal carcinoma. The Journal of Pathology, 217(3), 345-352. https://doi.org/10.1002/path.2487

@article{e173a77b90e94a00b9409bbc587f45d3,

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 γ-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.",

keywords = "ATM, Epstein-Barr virus, Nasopharyngeal carcinoma",

author = "Shikha Bose and Yap, {Lee Fah} and Matthew Fung and Jane Starzcynski and Amyza Saleh and Susan Morgan and Christopher Dawson and Chukwuma, {Marilyn B.} and Esther Maina and Maike Buettner and Wenbin Wei and John Arrand and Lim, {Paul V.H.} and Young, {Lawrence S.} and Teo, {Soo Hwang} and Tatjana Stankovic and Woodman, {Ciaran B.J.} and Murray, {Paul G.}",

year = "2009",

month = feb,

doi = "10.1002/path.2487",

language = "English",

volume = "217",

pages = "345--352",

journal = "The Journal of Pathology",

issn = "0022-3417",

number = "3",

}

Bose, S, Yap, LF, Fung, M, Starzcynski, J, Saleh, A, Morgan, S, Dawson, C, Chukwuma, MB, Maina, E, Buettner, M, Wei, W, Arrand, J, Lim, PVH, Young, LS, Teo, SH, Stankovic, T, Woodman, CBJ & Murray, PG 2009, 'The ATM tumour suppressor gene is down-regulated in EBV-associated nasopharyngeal carcinoma', The Journal of Pathology, vol. 217, no. 3, pp. 345-352. https://doi.org/10.1002/path.2487

TY - JOUR

T1 - The ATM tumour suppressor gene is down-regulated in EBV-associated nasopharyngeal carcinoma

AU - Bose, Shikha

AU - Yap, Lee Fah

AU - Fung, Matthew

AU - Starzcynski, Jane

AU - Saleh, Amyza

AU - Morgan, Susan

AU - Dawson, Christopher

AU - Chukwuma, Marilyn B.

AU - Maina, Esther

AU - Buettner, Maike

AU - Wei, Wenbin

AU - Arrand, John

AU - Lim, Paul V.H.

AU - Young, Lawrence S.

AU - Teo, Soo Hwang

AU - Stankovic, Tatjana

AU - Woodman, Ciaran B.J.

AU - Murray, Paul G.

PY - 2009/2

Y1 - 2009/2

N2 - 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 γ-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.

AB - 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 γ-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.

KW - ATM

KW - Epstein-Barr virus

KW - Nasopharyngeal carcinoma

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U2 - 10.1002/path.2487

DO - 10.1002/path.2487

M3 - Article

C2 - 19142888

AN - SCOPUS:60549116871

SN - 0022-3417

VL - 217

SP - 345

EP - 352

JO - The Journal of Pathology

JF - The Journal of Pathology

IS - 3

ER -

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

Abstract

Keywords

UN SDGs

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