Cross-talk between c-Jun/Ets1 involved in EB virus-encoded latent membrane protein 1 regulates expression of matrix metalloproteinase-9 in nasopharyngeal carcinoma.
- Author:
Liang ZENG
1
;
Yi-ping LIU
;
Yong-guang TAO
;
Mi-dan AI
;
Xiao-rong ZHAO
;
Ya CAO
Author Information
- Publication Type:Journal Article
- MeSH: Herpesvirus 4, Human; genetics; Humans; Matrix Metalloproteinase 9; biosynthesis; genetics; Nasopharyngeal Neoplasms; metabolism; virology; Proto-Oncogene Protein c-ets-1; genetics; Proto-Oncogene Proteins c-jun; genetics; Transfection; Tumor Cells, Cultured; Viral Matrix Proteins; genetics
- From: Chinese Journal of Oncology 2005;27(4):204-208
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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.
METHODSSite-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.
RESULTSThe 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.
CONCLUSIONThe 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.
