RECK negatively regulates matrix metalloproteinase-9 transcription.
RECK, a glycosylphosphatidylinositol-anchored glycoprotein, inhibits the enzymatic activities of some matrix metalloproteinases (MMP), thereby suppressing tumor cell metastasis; however, the detailed mechanism is still obscure. In this study, we compared the gene expression profiles between mock- and RECK-transfected HT1080 cells and showed that RECK decreases MMP-9 mRNA levels but not other MMP mRNA levels. Moreover, treatment with RECK-specific siRNA increased MMP-9 mRNA in RECK-expressing cells. The promoter assay showed that MMP-9 promoter activity was suppressed by RECK and that RECK-mediated suppression of MMP-9 promoter activity requires 12-O-tetradecanoylphorbol-13-acetate-responsive element (TRE) and kappaB sites. Moreover, the binding ability of Fra-1 and c-Jun to TRE within the MMP-9 promoter region was suppressed by RECK. Thus, these results show that RECK is a negative regulator of MMP-9 transcription.
Takagi
Satoshi
S
Antibiotics Laboratory and Chemical Biology Department, Advanced Science Institute, RIKEN and Graduate School of Science and Engineering, Saitama University, Saitama, Japan.
Simizu
Siro
S
Osada
Hiroyuki
H
D002460:Cell Line; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D005354:Fibrosarcoma; D058851:GPI-Linked Proteins; D015971:Gene Expression Regulation, Enzymologic; D017930:Genes, Reporter; D006801:Humans; D008168:Lung; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics*; D016328:NF-kappa B / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D010957:Plasmids; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; C115460:RECK protein, human; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate