Bcl-2 proto-oncogene expression in Epstein-Barr-virus-associated nasopharyngeal carcinoma.
The bcl-2 proto-oncogene product inhibits apoptosis. Increased levels of bcl-2 protein are associated with prolonged B-cell survival and have been demonstrated in a high proportion of follicular B-cell lymphoma. Recent studies have shown that bcl-2 protein expression in B cells immortalized by Epstein-Barr virus (EBV) in vitro is up-regulated by the EBV-latency-associated antigen, latent membrane protein (LMP) 1. The epithelial malignancy, undifferentiated nasopharyngeal carcinoma (UNPC), has a well-established association with EBV and the tumour cells characteristically display a restricted latent viral phenotype including LMP 1. This study has investigated the relationship between the presence of EBV DNA, EBV phenotypic profiles and bcl-2 protein expression in conventionally processed and cryopreserved samples of NPC using in situ hybridization, immunocytochemical and immunoblotting techniques. bcl-2 was detected in most (80%) samples of UNPC as well as in 1/3 samples of keratinizing NPC and 2/2 samples of nasopharyngeal adenocarcinoma. However, no close correlation was found between the presence of EBV DNA, and profiles for LMP 1 and bcl-2 protein expression in 45 UNPC. In addition, bcl-2 protein was shown to be selectively expressed in the basal compartment of normal nasopharyngeal epithelia. bcl-2 protein expression has not been reported previously in malignant tumours of epithelial origin. The findings in this study implicate a role for bcl-2 both in normal keratinocyte differentiation and in the pathogenesis of epithelial malignancy.
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Histopathology Unit, Imperial Cancer Research Fund, London, UK.
Elia
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G
Lucas
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Thomas
J A
JA
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D004279:DNA, Viral / Q000032:analysis*; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D009305:Nasopharynx / Q000737:chemistry; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D019253:Proto-Oncogene Proteins c-bcl-2; D011519:Proto-Oncogenes / Q000235:genetics*
D004279:DNA, Viral; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2