Expression of Epstein–Barr virus (EBV)-encoded latent membrane proteins and STAT3 activation in nasopharyngeal carcinoma

Abstract

The Epstein-Barr virus (EBV) is associated with virtually all cases of undifferentiated nasopharyngeal carcinoma (NPC), and it was proposed that the EBV-encoded transforming protein, latent membrane protein (LMP) 1, may play a role in the neoplastic process. It was proposed recently that LMP1 expression in epithelial cells may be regulated through a loop involving activated signal transducer and activator of transcription 3 (STAT3), LMP1, LMP1-mediated induction of interleukin (IL)-6 expression and STAT3 activation through the IL-6 receptor. This autoregulatory loop may be suppressed by another viral protein, LMP2A, an effect which in turn can be overcome by exogenous IL-6. Here we show that, as expected, expression of LMP1 and LMP2A tend to be exclusive in NPC tumours. Rare cases showing a co-expression of both proteins can be explained by STAT3 activation via the receptors for IL-6 or epidermal growth factor. STAT3 activation was a consistent feature of NPC tumour cells. However, in most cases, this was not accompanied by detectable expression of LMP1, suggesting either that LMP2A expression may suffice to suppress LMP1 expression or that additional factors may be operational. This study emphasises the need to correlate in vitro results with observational studies of ex vivo tumour tissues.