Cross-talk between c-Jun/Ets1 involved in EB virus-encoded latent membrane protein 1 regulates expression of matrix metalloproteinase-9 in nasopharyngeal carcinoma
Zeng, L.; Liu, Y-ping.; Tao, Y-guang.; Ai, M-dan.; Zhao, X-rong.; Cao, Y.
Zhonghua Zhong Liu Za Zhi 27(4): 204-208
2005
ISSN/ISBN: 0253-3766 PMID: 15949416 Document Number: 589095
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 protein1 (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(-53.3)/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 c4un or Ets1 antisense oligonucleotides, activity of MMP-9 induced by LMP1 decreased significantly, especially with combined blockade of c4un and Ets1. Conclusion 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.