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

Shikha Bose; LF Yap; Matthew Fung; J Starzcynski; A Saleh; S Morgan; Christopher Dawson; MB Chukwuma; E Maina; M Buettner; Wenbin Wei; John Arrand; PV Lim; Lawrence Young; SH Teo; Tatjana Stankovic; Ciaran Woodman; Paul Murray

doi:10.1002/path.2487

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

Shikha Bose, LF Yap, Matthew Fung, J Starzcynski, A Saleh, S Morgan, Christopher Dawson, MB Chukwuma, E Maina, M Buettner, Wenbin Wei, John Arrand, PV Lim, Lawrence Young, SH Teo, Tatjana Stankovic, Ciaran Woodman, Paul Murray

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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.

Original language	English
Pages (from-to)	345-52
Number of pages	8
Journal	Journal of Pathology
Volume	217
Issue number	3
DOIs	https://doi.org/10.1002/path.2487
Publication status	Published - 1 Feb 2009

Keywords

Epstein-Barr virus
nasopharyngeal carcinoma
ATM

UN SDGs

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

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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, PV., Young, L., Teo, SH., Stankovic, T., Woodman, C., & Murray, P. (2009). The ATM tumour suppressor gene is down-regulated in EBV-associated nasopharyngeal carcinoma. Journal of Pathology, 217(3), 345-52. https://doi.org/10.1002/path.2487

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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.",

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

author = "Shikha Bose and LF Yap and Matthew Fung and J Starzcynski and A Saleh and S Morgan and Christopher Dawson and MB Chukwuma and E Maina and M Buettner and Wenbin Wei and John Arrand and PV Lim and Lawrence Young and SH Teo and Tatjana Stankovic and Ciaran Woodman and Paul Murray",

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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, PV, Young, L, Teo, SH, Stankovic, T, Woodman, C & Murray, P 2009, 'The ATM tumour suppressor gene is down-regulated in EBV-associated nasopharyngeal carcinoma.', Journal of Pathology, vol. 217, no. 3, pp. 345-52. 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, LF

AU - Fung, Matthew

AU - Starzcynski, J

AU - Saleh, A

AU - Morgan, S

AU - Dawson, Christopher

AU - Chukwuma, MB

AU - Maina, E

AU - Buettner, M

AU - Wei, Wenbin

AU - Arrand, John

AU - Lim, PV

AU - Young, Lawrence

AU - Teo, SH

AU - Stankovic, Tatjana

AU - Woodman, Ciaran

AU - Murray, Paul

PY - 2009/2/1

Y1 - 2009/2/1

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 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.

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 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.

KW - Epstein-Barr virus

KW - nasopharyngeal carcinoma

KW - ATM

U2 - 10.1002/path.2487

DO - 10.1002/path.2487

M3 - Article

C2 - 19142888

SN - 1096-9896

VL - 217

SP - 345

EP - 352

JO - Journal of Pathology

JF - 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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