Takagi Satoshi, Simizu Siro, Osada Hiroyuki
Antibiotics Laboratory and Chemical Biology Department, Advanced Science Institute, RIKEN and Graduate School of Science and Engineering, Saitama University, Saitama, Japan.
Cancer Res. 2009 Feb 15;69(4):1502-8. doi: 10.1158/0008-5472.CAN-08-2635. Epub 2009 Feb 10.
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.
RECK是一种糖基磷脂酰肌醇锚定糖蛋白，可抑制某些基质金属蛋白酶（MMP）的酶活性，从而抑制肿瘤细胞转移；然而，其详细机制仍不清楚。在本研究中，我们比较了mock转染和RECK转染的HT1080细胞之间的基因表达谱，结果显示RECK可降低MMP-9 mRNA水平，但不影响其他MMP mRNA水平。此外，用RECK特异性siRNA处理可增加表达RECK的细胞中的MMP-9 mRNA。启动子分析表明，RECK可抑制MMP-9启动子活性，且RECK介导的MMP-9启动子活性抑制需要12-O-十四烷酰佛波醇-13-乙酸酯反应元件（TRE）和κB位点。此外，RECK可抑制Fra-1和c-Jun与MMP-9启动子区域内TRE的结合能力。因此，这些结果表明RECK是MMP-9转录的负调节因子。
