Fra-1 and Stat3 synergistically regulate activation of human MMP-9 gene.
Fra-1 is overexpressed in a variety of human tumors. Whether MMP-9 expression is regulated by Fra-1 has been contradictory. To clarify the capability of Fra-1 in activating transcription of MMP-9 gene, we analyzed the transcriptional activity of the MMP-9 promoter through the measure of luciferase activities in the MCF-7 cells transiently transfected with Fra-1. The positive regulation of Fra-1 on MMP-9 promoter was not detectable. By the analysis of MMP-9 promoter, a potential Stat3 binding site, just juxtaposed AP-1 consensus sequence, was noticed. The reporter assay showed that MMP-9 promoter was activated remarkably by cotransfection with Fra-1 and Stat3C. DNA affinity precipitation assay confirmed the binding of Stat3 and Fra-1 to the elements of MMP-9 promoter and also revealed c-Jun recruited to Stat3-Fra-1 complex. By immunoprecipitation assay, the Stat3/Fra-1, Stat3/c-Jun and Fra-1/c-Jun complexes were identified in vivo. Our study demonstrated that the activation of MMP-9 promoter is dependent upon interactions of Fra-1/c-Jun with Stat3. A juxtaposed Stat3/AP-1 element plays a crucial role in the manner of enhancersome in the activation of MMP-9 gene. The functional cooperation of the Stat3 and AP-1 transcription factors is required for the transcription of MMP-9 gene.
Song
Yuhua
Y
Institute of Basic Medical Sciences, Beijing 100850, PR China.
Qian
Lu
L
Song
Santai
S
Chen
Liyong
L
Zhang
Yan
Y
Yuan
Guogang
G
Zhang
Hao
H
Xia
Qing
Q
Hu
Meiru
M
Yu
Ming
M
Shi
Ming
M
Jiang
Zefei
Z
Guo
Ning
N
D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics; D000099169:Fos-Related Antigen 1
D020780:Matrix Metalloproteinase 9; D016760:Proto-Oncogene Proteins c-fos; D050796:STAT3 Transcription Factor; D000099169:Fos-Related Antigen 1