期刊
NEOPLASIA
卷 8, 期 11, 页码 967-977出版社
NEOPLASIA PRESS
DOI: 10.1593/neo.06574
关键词
chemotherapy; H-Ras; NF-kappa B; neuroblastoma; p53
类别
资金
- NCI NIH HHS [CA697276-04] Funding Source: Medline
- NHLBI NIH HHS [2T32HL07622, T32 HL007622] Funding Source: Medline
- NHLBI NIH HHS [2T32HL07622] Funding Source: Medline
Neuroblastic (N) type neuroblastoma ( NB) is the predominant cell type in NB tumors. Previously, we determined that activated nuclear factor kappa B (NF-kappa B) is required for doxorubicin and etoposide to kill N-type NB cells. This study was undertaken to determine how NF kappa B is activated by these agents. The results show that p53 protein levels increase within 15 to 30 minutes of treatment. This increase occurs before the degradation of inhibitor of NF-kappa B (I-kappa B) A and the NF-kappa B-dependent activation of gene transcription. Moreover, p53 is necessary for NF-kappa B activation because cells with inactive p53 were resistant to NF-kappa B-mediated cell death. This pathway was further defined to show that p53 leads to the activation of MAPK/ERK activity kinase (MEK) 1 through a process that depends on protein synthesis and H-Ras. MEK1, in turn, mediates I-kappa B kinase activation. Together, these results demonstrate for the first time how NF-kappa B is activated in NB cells in response to conventional drugs. Furthermore, these findings provide an explanation as to why H-Ras expression correlates with a favorable prognosis in NB and identify intermediary signaling molecules that are targets for discovering treatments for NB that is resistant to conventional agents.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据