[Cross-talk between c-Jun/Ets1 involved in EB virus-encoded latent membrane protein 1 regulates expression of matrix metalloproteinase-9 in nasopharyngeal carcinoma].
OBJECTIVE
To investigate effect of AP-1 and Ets binding site adjacent to matrix metalloproteinase-9 (MMP-9) promoter on activation of MMP-9 transcription of nasopharyngeal carcinoma cells transfected with EBV-encoded latent membrane protein 1 (LMP1), and to ascertain if cross-talk between c-Jun and Ets1 is involved in LMP1-regulating expression of MMP-9.


METHODS
Site-directed mutagenesis technique was used to establish a series of mutants, including MMP-9-CAT-Ets(-540)mt, MMP-9-CAT-AP-1(-533)mt and MMP-9-CAT-AP-1(-533)/Ets(-540)mt. After the mutants were transfected into LMP1-expressing NPC HNE2 cells regulated by Tet-on system (pTet-on-LMP1 HNE2), CAT activity of these mutants were assayed with induction of LMP1. With blockade of c-Jun or Ets1 antisense oligonucleotides, the activity of MMP-9 induced by LMP1 was assayed with gelatin zymography.


RESULTS
The CAT activity of MMP-9-Ets(-540)mt-CAT, MMP-9-AP-1(-533)mt-CAT, MMP-9-AP-1(-533)/Ets(-540) mt-CAT decreased significantly compared to MMP-9-CAT wt. After blockade with c-Jun or Ets1 antisense oligonucleotides, activity of MMP-9 induced by LMP1 decreased significantly, especially with combined blockade of c-Jun and Ets1.


CONCLUSIONS
The results suggest that transcription factor AP-1 and Ets play an crucial role in activation of MMP-9 transcription induced by LMP1, and cross-talk between c-Jun/Ets1 is involved in expression of MMP-9 mediated by LMP1.
Zeng
Liang
L
Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha 410078, China.
Liu
Yi-ping
YP
Tao
Yong-guang
YG
Ai
Mi-dan
MD
Zhao
Xiao-rong
XR
Cao
Ya
Y
D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000821:virology; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000235:genetics*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; C494041:ETS1 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D016755:Proto-Oncogene Proteins c-jun; D014763:Viral Matrix Proteins; D020780:Matrix Metalloproteinase 9