論文 - 詳細
| RRC ID | 52080 |
|---|---|
| 著者 | Mori J, Tanikawa C, Ohnishi N, Funauchi Y, Toyoshima O, Ueda K, Matsuda K. |
| タイトル | EPSIN 3, A Novel p53 Target, Regulates the Apoptotic Pathway and Gastric Carcinogenesis. |
| ジャーナル | Neoplasia |
| Abstract |
BACKGROUND & AIM:p53 activation by cellular stresses induces the transcription of hundreds of its target genes. To elucidate the entire picture of its downstream pathway, we screened a cDNA microarray dataset of adriamycin-treated HCT116 p53-/- or p53+/+ cells and identified EPSIN 3 as a novel p53 target. METHODS:Potential p53 binding sequences in the EPSIN 3 locus were evaluated by reporter and CHIP assays. To investigate the role of EPSIN 3 in the p53 downstream pathway, we assessed DNA damage-induced apoptosis in EPSIN 3-knockdown HCT116 cells or Epsin 3-deficient mice. In addition, we evaluated EPSIN 3 expression levels in various tissues, including gastric adenocarcinoma, human gastric mucosa with or without Helicobacter pylori infection, and mouse acute gastritis tissues induced by indomethacin. RESULTS:In response to DNA damage, p53 induced the expression of EPSIN 3 through the p53 binding elements in the EPSIN 3 promoter and the first intron. Knockdown of EPSIN 3 resulted in resistance to DNA damage-induced apoptosis both in vitro and in vivo. EPSIN 3 expression was down-regulated in gastric cancer tissues compared with normal tissues. In addition, Helicobacter pylori infection and indomethacin-induced acute gastritis repressed EPSIN 3 expression in gastric mucosa. CONCLUSIONS:EPSIN 3 is a novel p53 target and a key mediator of apoptosis. Chronic or acute mucosal inflammation as well as p53 inactivation induced down-regulation of EPSIN 3 and subsequently caused apoptosis resistance, which is a hallmark of cancer cells. |
| 巻・号 | 19(3) |
| ページ | 185-195 |
| 公開日 | 2017-3-1 |
| DOI | 10.1016/j.neo.2016.12.010 |
| PII | S1476-5586(16)30151-8 |
| PMID | 28152424 |
| PMC | PMC5288315 |
| MeSH | Adaptor Proteins, Vesicular Transport / genetics* Apoptosis / genetics* Cell Line Cell Proliferation Cell Transformation, Neoplastic / genetics* Cell Transformation, Neoplastic / metabolism* Gastritis / genetics Gastritis / metabolism Gastritis / microbiology Gastritis / pathology Gene Expression Regulation, Neoplastic Gene Knockout Techniques HCT116 Cells Humans Protein Binding Proteolysis Signal Transduction* Stomach Neoplasms / genetics* Stomach Neoplasms / metabolism* Stomach Neoplasms / pathology Stress, Physiological Tumor Suppressor Protein p53 / genetics Tumor Suppressor Protein p53 / metabolism* |
| IF | 5.696 |
| 引用数 | 7 |
| リソース情報 | |
| ヒト・動物細胞 | 293T(RCB2202) |