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学科主题: 基础医学
题名:
Alpha fetoprotein is a novel protein-binding partner for caspase-3 and blocks the apoptotic signaling pathway in human hepatoma cells
作者: Li, Mengsen1,2; Li, Hui1; Li, Chaoying1; Zhou, Sheng2; Guo, Liyuan1; Liu, Han1; Jiang, Wei1; Liu, Xinhua1; Li, Pingfeng1; McNutt, Michael A.3; Li, Gang1
关键词: alpha fetoprotein ; all-trans retinoic acid ; TNF-related apoptosis-inducing ligand ; caspase-3 ; hepatocellular carcinoma cells ; apoptosis
刊名: INTERNATIONAL JOURNAL OF CANCER
发表日期: 2009-06-15
DOI: 10.1002/ijc.24272
卷: 124, 期:12, 页:2845-2854
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: HEPATOCELLULAR-CARCINOMA CELLS ; TRAIL-INDUCED APOPTOSIS ; OPIOID RECEPTOR GENE ; CANCER CELLS ; HEPATOCARCINOMA CELLS ; GASTRIC-CANCER ; IN-VITRO ; LIGAND ; EXPRESSION ; DEATH
英文摘要:

Although there is increasing evidence that alpha fetoprotein (AFP) may function as regulatory factor in the growth of tumor cells, the precise mechanism is still unclear. In the current study, we investigated the role of the cytoplasmic AFP in caspase-3-mediated signaling of apoptosis. Our results showed that low (loses of TNF-related apoptosis-inducing ligand (TRAIL) elevated the activity of caspase-8, but not caspase-3. Caspase-3 colocalized and interacted with AFP in the cytoplasm of Bel 7402 cells, and translocated into nuclei in association with the occurrence of apoptosis while cells were under cotreatment with all-trans retinoic acid (ATRA) or TRAIL. AFP was able to form complexes with caspase-3 and block onward transmission of signaling from caspase-8. Knockdown of AFP increased the sensitivity of Bel 7402 cells to TRAIL, and thereby, triggered caspase-3 signaling. No intermolecule interaction occurred between AFP and caspase-8, nor was caspase-8 activity altered after AFP knockdown, demonstrating the selectivity of AFP in interfering with the apoptotic signaling pathway. The effect of AFP on caspase-3 was further confirmed by transfection of the AFP gene into HLE cells (AFP negative). We conclude that ATRA or TRAIL resistance in AFP producing hepatoma is at least, in part, attributable to the high level of the cytoplasmic AFP. Therefore, it is possible that the combination of AFP gene silencing together with ATRA/TRAIL cotreatment will benefit the enhancement of the chemotherapeutic efficiency of these agents on tumors. (C) 2009 UICC

语种: 英语
所属项目编号: 30621002 ; 30671856 ; 30772536 ; 30660071 ; 30760090 ; 20070001735
项目资助者: National Natural Science Foundation of China ; Foundation of National Education Ministry
WOS记录号: WOS:000265997500011
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64713
Appears in Collections:基础医学院_病理学系_期刊论文

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作者单位: 1.Hainan Med Coll, Key Lab Mol Biol, Haikou, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Beijing 100083, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Dept Pathol, Beijing 100083, Peoples R China

Recommended Citation:
Li, Mengsen,Li, Hui,Li, Chaoying,et al. Alpha fetoprotein is a novel protein-binding partner for caspase-3 and blocks the apoptotic signaling pathway in human hepatoma cells[J]. INTERNATIONAL JOURNAL OF CANCER,2009,124(12):2845-2854.
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