論文 - 詳細
| RRC ID | 18940 |
|---|---|
| 著者 | Hosono T, Tanaka T, Tanji K, Nakatani T, Kamitani T. |
| タイトル | NUB1, an interferon-inducible protein, mediates anti-proliferative actions and apoptosis in renal cell carcinoma cells through cell-cycle regulation. |
| ジャーナル | Br J Cancer |
| Abstract |
BACKGROUND:NEDD8 ultimate buster 1 (NUB1) is an interferon (IFN)-inducible protein that downregulates NEDD8 expression and its conjugation system. Although overexpression of NUB1 induces a growth-inhibitory effect in cells, the mechanisms underlying the anti-mitogenic actions of NUB1 in cancer cells remain uncertain. We investigated the anti-cancer effects of NUB1 in human renal cell carcinoma (RCC) cells. METHODS:Nine human RCC cells were used for this study. The proliferation of RCC cells exposed to IFN-alpha was measured by water-soluble tetrazolium salt assay. The expression level of NUB1 in cells was measured by quantitative reverse transcriptase PCR or western blot analysis. Apoptosis and cell-cycle analysis were performed by flow cytometry. Silencing of NUB1 was performed using a small interfering RNA. RESULTS:Both NUB1 messenger RNA and protein were significantly induced by IFN-alpha in seven out of nine selected RCC cell lines, and the NUB1 expressions induced by IFN-alpha correlated positively with cell growth inhibition. Overexpression of NUB1 remarkably induced S-phase transition during cell cycle and apoptosis in IFN-alpha-resistant A498 cells, in which NUB1 is not induced by IFN-alpha. The expression levels of two cell-cycle regulator proteins, cyclin E and p27, were increased under the aforementioned conditions. The knockdown of NUB1 enhanced cell proliferation of IFN-alpha-resistant A498 cells and suppressed IFN-alpha-induced growth inhibition in IFN-alpha-sensitive 4TUHR cells. CONCLUSION:NUB1 may be a key factor involved not only in cell growth inhibition by IFN-alpha in RCC cells but also in the anti-cancer effect against IFN-alpha-resistant RCC cells. |
| 巻・号 | 102(5) |
| ページ | 873-82 |
| 公開日 | 2010-3-2 |
| DOI | 10.1038/sj.bjc.6605574 |
| PII | 6605574 |
| PMID | 20160729 |
| PMC | PMC2833260 |
| MeSH | Adaptor Proteins, Signal Transducing Apoptosis* Blotting, Western Carcinoma, Renal Cell / drug therapy Carcinoma, Renal Cell / metabolism Carcinoma, Renal Cell / pathology* Cell Line, Tumor Cell Proliferation* Cyclin E / genetics Cyclin E / metabolism Cyclin-Dependent Kinase Inhibitor p27 / genetics Cyclin-Dependent Kinase Inhibitor p27 / metabolism Humans Interferon-alpha / pharmacology* Kidney Neoplasms / drug therapy Kidney Neoplasms / metabolism Kidney Neoplasms / pathology* Oncogene Proteins / genetics Oncogene Proteins / metabolism RNA, Messenger / genetics RNA, Messenger / metabolism RNA, Small Interfering / pharmacology Reverse Transcriptase Polymerase Chain Reaction S Phase* Transcription Factors / antagonists & inhibitors Transcription Factors / genetics Transcription Factors / metabolism* |
| IF | 5.791 |
| 引用数 | 15 |
| WOS 分野 | ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | RCC10RGB(RCB1151) OS-RC-2(RCB0735) TUHR4TKB (RCB1198) |