A20 RNA expression is associated with undifferentiated nasopharyngeal carcinoma and poorly differentiated head and neck squamous cell carcinoma.
A20 is an anti-apoptotic gene that can be induced in human epithelial cell lines in response to expression of the Epstein-Barr virus (EBV) gene product latent membrane protein 1 (LMP1). EBV is a ubiquitous, persistent human herpesvirus that is consistently associated with undifferentiated nasopharyngeal carcinoma (NPC), in which antigen expression includes LMP1. Consistent with a potential role in the development of NPC, LMP1 has profound effects on epithelial cell growth. A20 may be a key downstream effector of LMP1 in NPC, as LMP1-induced A20 blocks p53-mediated apoptosis in H1299 epithelial cells and most NPCs have wild-type p53. Moreover, the potential role of A20 in the development of epithelial malignancies may extend to tumours not associated with EBV. The purpose of this study was to develop an in situ hybridization assay to assess expression of A20 RNA in undifferentiated NPC and in non-EBV-associated poorly differentiated head and neck squamous cell carcinomas (SCCs) and well-differentiated SCCs of the skin. A20 RNA expression was also examined in normal samples of oral mucosa and skin. Expression of A20 was demonstrated in 76 per cent of undifferentiated NPCs and in 80 per cent of poorly differentiated head and neck SCCs, suggesting a role for A20 in the pathogenesis of these epithelial malignancies. By contrast, A20 RNA was not detected in well-differentiated SCCs of the skin, or in any normal samples of squamous epithelial tissue. The pathway leading to A20 expression in non-EBV-associated poorly differentiated head and neck SCCs is clearly LMP1-independent. LMP1 expression was demonstrated in 29 per cent of NPC biopsies, suggesting an LMP1-independent pathway to A20 induction in undifferentiated NPC.
Department of Histopathology, King's College School of Medicine and Dentistry, Bessemer Road, London SE5 9PJ, U.K.
J D
JD
Codd
J R
JR
Salisbury
G
G
Packham
L J
LJ
Nicholson
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D002454:Cell Differentiation; D003546:Cysteine Endopeptidases; D004268:DNA-Binding Proteins; D004622:Embryo, Mammalian / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism / Q000821:virology; D015870:Gene Expression; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000378:metabolism; D012269:Ribosomal Proteins; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D014763:Viral Matrix Proteins / Q000378:metabolism; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; D011506:Proteins; D012334:RNA, Neoplasm; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; D014763:Viral Matrix Proteins; C067169:RPL22 protein, human; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D003546:Cysteine Endopeptidases; C513261:Tnfaip3 protein, mouse