Expression of tumor necrosis factor receptor-associated factor 1 in nasopharyngeal carcinoma: possible upregulation by Epstein-Barr virus latent membrane protein 1.
EBV infection is associated with virtually all cases of undifferentiated NPC, and the EBV-encoded LMP1 is expressed in a proportion of cases. LMP1 has transforming functions similar to members of the TNF receptor family and activates intracellular signaling cascades through interaction with TRAFs. In B cells, expression of TRAF1 is in turn upregulated by LMP1. LMP1 signaling in epithelial cells may be affected by the presence or absence of TRAF1. By immunohistochemistry, we detected TRAF1 expression in 17 of 42 (40%) EBV+ undifferentiated NPCs. All 7 LMP1+ NPC biopsies were also TRAF1+. Using an RNAse protection assay, high-level TRAF1 expression was detected in an LMP1-expressing NPC-derived cell line (C15) and expression was weaker in 2 LMP1- cell lines (C17, C19). Finally, LMP1 upregulated TRAF1 expression in an EBV- keratinocyte cell line. Our results demonstrate that TRAF1 is expressed in NPC tumor cells in vivo and suggest that TRAF1 expression may be upregulated by LMP1 in NPC. An antiapoptotic function has been proposed for TRAF1, and this may be relevant for the pathogenesis of NPC.
Siegler
Gabriele
G
Institute for Pathology, Friedrich-Alexander-University, Erlangen, Germany.
Meyer
Birgit
B
Dawson
Chris
C
Brachtel
Elena
E
Lennerz
Jochen
J
Koch
Claudia
C
Kremmer
Elisabeth
E
Niedobitek
Edith
E
Gonnella
Roberta
R
Pilch
Ben Z
BZ
Young
Lawrence S
LS
Niedobitek
Gerald
G
D000956:Antigens, Viral; D017209:Apoptosis; D002213:Capsid; D002277:Carcinoma / Q000235:genetics* / Q000503:physiopathology / Q000821:virology*; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000503:physiopathology / Q000821:virology*; D014176:Protein Biosynthesis; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D047990:TNF Receptor-Associated Factor 1; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D014763:Viral Matrix Proteins / Q000494:pharmacology*
D000956:Antigens, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D047990:TNF Receptor-Associated Factor 1; D014763:Viral Matrix Proteins