論文 - 詳細
| RRC ID | 44925 |
|---|---|
| 著者 | Yamaguchi Y, Takenobu H, Ohira M, Nakazawa A, Yoshida S, Akita N, Shimozato O, Iwama A, Nakagawara A, Kamijo T. |
| タイトル | Novel 1p tumour suppressor Dnmt1-associated protein 1 regulates MYCN/ataxia telangiectasia mutated/p53 pathway. |
| ジャーナル | Eur J Cancer |
| Abstract |
Neuroblastoma (NB) is a paediatric solid tumour which originates from sympathetic nervous tissues. Deletions in chromosome 1p are frequently found in unfavourable NBs and are correlated with v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) amplification; however, it remains to be elucidated how the 1p loss contributes to MYCN-related oncogenic processes in NB. In this study, we identified the role of Dnmt1-associated protein 1 (DMAP1), coded on chromosome 1p34, in the processes. We studied the expression and function of DMAP1 in NB and found that low-level expression of DMAP1 related to poor prognosis, unfavourable histology and 1p Loss of heterozygosity (LOH) of primary NB samples. Intriguingly, DMAP1 induced ataxia telangiectasia mutated (ATM) phosphorylation and focus formation in the presence of a DNA damage reagent, doxorubicin. By DMAP1 expression in NB and fibroblasts, p53 was activated in an ATM-dependent manner and p53-downstream pro-apoptotic Bcl-2 family molecules were induced at the mRNA level, resulting in p53-induced apoptotic death. BAX and p21(Cip1/Waf1) promoter activity dependent on p53 was clearly up-regulated by DMAP1. Further, MYCN transduction in MYCN single-copy NB cells accelerated doxorubicin (Doxo)-induced apoptotic cell death; MYCN is implicated in DMAP1 protein stabilisation and ATM phosphorylation in these situations. DMAP1 knockdown attenuated MYCN-dependent ATM phosphorylation and NB cell apoptosis. Together, DMAP1 appears to be a new candidate for a 1p tumour suppressor and its reduction contributes to NB tumourigenesis via inhibition of MYCN-related ATM/p53 pathway activation. |
| 巻・号 | 50(8) |
| ページ | 1555-65 |
| 公開日 | 2014-5-1 |
| DOI | 10.1016/j.ejca.2014.01.023 |
| PII | S0959-8049(14)00096-3 |
| PMID | 24559687 |
| MeSH | Apoptosis Ataxia Telangiectasia / metabolism* Ataxia Telangiectasia Mutated Proteins / metabolism* Cell Line, Tumor Child, Preschool Fibroblasts / metabolism Humans Infant N-Myc Proto-Oncogene Protein Neuroblastoma / metabolism* Nuclear Proteins / metabolism* Oncogene Proteins / metabolism* Phosphorylation Prognosis Repressor Proteins / physiology* Signal Transduction Survival Analysis Tumor Suppressor Protein p53 / metabolism* |
| IF | 7.275 |
| 引用数 | 8 |
| WOS 分野 | ONCOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | CHP-134(RCB0487) |