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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Fujii, Satoshi Ochiai, Atsushi Ito, Kosei Ito, Yoshiaki |
| Description | Author Affiliation: Fujii S ( Pathology Division, Research Center for Innovative Oncology, National Cancer Center at Kashiwa, 6-5-1, Kashiwanoha, Kashiwa, Chiba 277-857 7 Japan.) |
| Abstract | Overexpression of enhancer of zeste homologue 2 (EZH2) occurs in various malignancies and is associated with a poor prognosis, especially because of increased cancer cell proliferation. In this study we found an inverse correlation between EZH2 and RUNX3 gene expression in five cancer cell lines, i.e. gastric, breast, prostate, colon, and pancreatic cancer cell lines. Chromatin immunoprecipitation assay showed an association between EZH2 bound to the RUNX3 gene promoter, and trimethylated histone H3 at lysine 27, and HDAC1 (histone deacetylase 1) bound to the RUNX3 gene promoter in cancer cells. RNA interference-mediated knockdown of EZH2 resulted in a decrease in H3K27 trimethylation and unbound HDAC1 and an increase in expression of the RUNX3 gene. Restoration of RUNX3 expression was not associated with any change in DNA methylation status in the RUNX3 promoter region. RUNX3 was repressed by histone deacetylation and hypermethylation of a CpG island in the promoter region and restored by trichostatin A or/and 5-aza-2′-deoxycytidine. Immunofluorescence staining confirmed restoration of expression of the RUNX3 protein after knockdown of EZH2 and its restoration resulted in decreased cell proliferation. In vivo, an inverse relationship between expression of the EZH2 and RUNX3 proteins was observed at the individual cell level in gastric cancer patients in the absence of DNA methylation in the RUNX3 promoter region. The results showed that RUNX3 is a target for repression by EZH2 and indicated an underlying mechanism of the functional role of EZH2 overexpression on cancer cell proliferation. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 25 |
| Volume Number | 283 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2008-06-20 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Core Binding Factor Alpha 3 Subunit Biosynthesis DNA-Binding Proteins Physiology Gene Expression Regulation, Neoplastic Histones Metabolism Stomach Neoplasms Transcription Factors Adenocarcinoma Cell Proliferation DNA Methylation Lysine Chemistry Polycomb Repressive Complex 2 Promoter Regions, Genetic Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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