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.

Three Epstein–Barr virus latency proteins independently promote genomic instability by inducing DNA damage, inhibiting DNA repair and inactivating cell cycle checkpoints

“…Reduced or absent ATM expression, resulting either from deletion of the ATM locus at chromosome 11q23 (Eclache et al, 2004) or methylation of the ATM promoter (Bolt et al, 2005), has been reported in a variety of tumors. Our finding that LMP-1 inhibits ATM expression is in line with the reported loss of Genomic instability in EBV-infected cells B Gruhne et al ATM in EBV-carrying tumors that express latency II such as NPC and HD (Bose et al, 2009). Interestingly, downregulation of ATM was shown to occur in HD independently of EBV carriage (Bose et al, 2007), suggesting that it may constitute a critical event in pathogenesis.…”

Integrated Analysis of Multiple Gene Expression Profiling Datasets Revealed Novel Gene Signatures and Molecular Markers in Nasopharyngeal Carcinoma

“…Moreover, because the genome-wide set of dysregulated genes and proteins are known to function in regulated biological networks or pathways associated with cancers, the focus of data obtained from gene expression profiling in cancers has been directed toward analysis of these sets of genes or pathways. In the literature, several reports have described dysregulation of gene expression in NPC and have found a vast amount of genome-wide information (3)(4)(5)(6)(7)(8)(9)(10)(11). However, the overall molecular signature of NPC is still undefined.…”

Up-Regulation of Lamin A/C Expression in Epstein-Barr Virus Immortalized B Cells and Burkitt Lymphoma Cell Lines of Activated B Cell Phenotype

“…The available data on B cell lines and NPCs are based on microarray experiments performed under variable experimental conditions [23,24].…”