[Increase of EGFR expression by Epstein-Barr virus LMP1 in nasopharyngeal carcinoma cells].
OBJECTIVE
To investigate the effect of LMP1 on the expression of epidermal growth factor receptor (EGFR) in HNE2-LMP1 cells.


METHODS
Stable transfectant HNE2 cell line expressing LMP1 (HNE2-LMP1) or its mutants (HNE2 del 187-351, HNE2 1-231, HNE2 1-187) were used as cell models. The expression of EGFR was detected by Western blot method. The characteristics of EGFR expression were analyzed when HNE2-LMP1 LMP1 cells were transiently transfected with TRAF1, 2, 3 or TRAF1, 2, 3 dominant negative mutants (DN-TRAF1, 2, 3). The growth characteristics of HNE2-LMP1 and vector controls were analyzed on serum-free media supplemented with EGF.


RESULTS
Stable expression of LMP1 in HNE2 cells increased the expression of EGFR. LMP1 CTAR1 domain, being identical to the TRAF interaction domain, was essential to the induction of EGFR. The CTAR2 domain did not induce expression of EGFR. Overexpression of either TRAF1, 3 or an dominant negative mutant of TRAF1, 3 inhibited the expression of EGFR, while TRAF2 or negative mutants of TRAF2 did slightly so. In HNE2-LMP1 cells, LMP1 expression increased the proliferative response to EGF while the vector control cells exhibited very low level of viability and did not proliferate.


CONCLUSIONS
The induction of EGFR by LMP1 CTAR1 may be an important component of EBV infection via an TRAF1, 2, 3 mechanism in the epithelial cells and may contribute to the development of epithelial malignancies such as nasopharyngeal carcinoma.
Wang
C
C
Cancer Institute, Hunan University, Changsha 410078, China.
Li
X
X
Gu
H
H
D015153:Blotting, Western; D002455:Cell Division / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009154:Mutation; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010957:Plasmids / Q000235:genetics; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000235:genetics / Q000502:physiology*
D018076:DNA, Complementary; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins; D066246:ErbB Receptors