The major cause of therapy failure and death of cancer patients is metastasis. RECK is a newly identified gene which was isolated by screening for human fibroblast cDNA clones giving rise to flat colonies when transfected into v-Ki-ras-transformed NIH3T3 cells. It can inhibit the release and activation of MMP-2 and MMP-9, and prevent cell invasion in vitro. In addition, RECK can repress tumor metastasis in experimental animal. Thus, RECK is a metastasis suppressor gene. However, RECK gene is a common target that is negatively regulated by oncogenic signals. Overexpression of c-myc protooncogene is frequently found in several types of human cancer and contributes to multiple steps of tumorigenesis. Ecto-expression of c-Myc in NIH3T3 cells inhibited RECK expression. Promoter activity assay suggested c-Myc repressed RECK at transcriptional level. By using DNA affinity precipitation assay and chromatin immunoprecipitation assay, we found that oncogenic c-Myc bound to the SP1 sites of RECK promoter in vitro and in vivo. It is possible that c-Myc could repress RECK expression via SP1. Our data suggest that c-Myc may inhibit the metastatic/angiogenic suppressor RECK to enhance cell invasiveness and restoration of RECK may be a novel strategy to inhibit c-Myc-mediated invasion.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0115107-130142 |
| Date | 15 January 2007 |
| Creators | Hsu, Hsiang-yi |
| Contributors | Wen-chun Hung, Ming-hong Tai, Hui-chiu Chang |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | Cholon |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0115107-130142 |
| Rights | campus_withheld, Copyright information available at source archive |
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