論文 - 詳細
| RRC ID | 66094 |
|---|---|
| 著者 | Ohashi T, Komatsu S, Ichikawa D, Miyamae M, Okajima W, Imamura T, Kiuchi J, Kosuga T, Konishi H, Shiozaki A, Fujiwara H, Okamoto K, Tsuda H, Otsuji E. |
| タイトル | Overexpression of PBK/TOPK relates to tumour malignant potential and poor outcome of gastric carcinoma. |
| ジャーナル | Br J Cancer |
| Abstract |
BACKGROUND:PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) is a serine-threonine kinase and overexpressed in various types of cancer by inhibiting the transactivation activities of p53 and PTEN. We tested whether PBK/TOPK acts as a cancer-promoting gene through its activation/overexpression in gastric cancer (GC). METHODS:We analysed five GC cell lines and 144 primary tumours, which were curatively resected in our hospital between 2001 and 2003. RESULTS:Overexpression of the PBK/TOPK protein was frequently detected in GC cell lines (4 out of 5 lines, 80.0%) was detected in primary tumour samples of GC (24 out of 144 cases, 16.6%) and was significantly correlated with venous invasion, tumour depth and recurrence rate. PDZ-binding kinase/T-LAK cell-originated protein kinase-overexpressing tumours had a worse survival rate than those with non-expressing tumours (P=0.0009, log-rank test). PDZ-binding kinase/T-LAK cell-originated protein kinase positivity was independently associated with a worse outcome in multivariate analysis (P<0.0001, hazard ratio 6.40 (2.71-14.49)). In PBK/TOPK-overexpressing GC cells, knockdown of PBK/TOPK inhibited the cell proliferation through the p53 activation in a TP53 mutation-dependent manner and inhibited the migration/invasion through the PTEN upregulation in a TP53 mutation-independent manner. CONCLUSIONS:These findings suggest PBK/TOPK plays a crucial role in tumour malignant potential through its overexpression and highlight its usefulness as a prognostic factor and potential therapeutic target in GC. |
| 巻・号 | 116(2) |
| ページ | 218-226 |
| 公開日 | 2017-1-17 |
| DOI | 10.1038/bjc.2016.394 |
| PII | bjc2016394 |
| PMID | 27898655 |
| PMC | PMC5243986 |
| MeSH | Adult Aged Aged, 80 and over Biomarkers, Tumor / genetics* Cell Line, Tumor Cell Proliferation / genetics Female Gene Expression Regulation, Neoplastic Humans Male Middle Aged Mitogen-Activated Protein Kinase Kinases / genetics* Neoplasm Invasiveness Prognosis Stomach Neoplasms / diagnosis* Stomach Neoplasms / genetics* Stomach Neoplasms / mortality Stomach Neoplasms / pathology Up-Regulation / genetics |
| IF | 5.791 |
| リソース情報 | |
| ヒト・動物細胞 | NUGC-4(RCB1939) HGC-27(RCB0500) |