Bose, Shikha, Yap, Lee-Fah, Fung, Matthew, Starzcynski, Jane, Saleh, Amyza, Morgan, Susan, Dawson, Christopher W., Chukwuma, Marilyn B., Maina, Esther, Buettner, Maike, Wei, Wenbin, Arrand, J. R. (John R.), Lim, Paul V. H., Young, Lawrence S., Teo, Soo Hwang, Stankovic, Tatjana, Woodman, Ciaran B. J. and Murray, Paul G.. (2009) The ATM tumour suppressor gene is down-regulated in EBV-associated nasopharyngeal carcinoma. Journal of Pathology, Vol.217 (No.3). pp. 345-352. ISSN 0022-3417

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.

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