IR@PKUHSC  > 北京大学基础医学院  > 病理学系
学科主题基础医学
Alpha fetoprotein is a novel protein-binding partner for caspase-3 and blocks the apoptotic signaling pathway in human hepatoma cells
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
2009-06-15
DOI10.1002/ijc.24272
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
资助者National Natural Science Foundation of China ; Foundation of National Education Ministry ; National Natural Science Foundation of China ; Foundation of National Education Ministry
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
资助者National Natural Science Foundation of China ; Foundation of National Education Ministry ; National Natural Science Foundation of China ; Foundation of National Education Ministry
WOS记录号WOS:000265997500011
Citation statistics
Cited Times:43[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/64713
Collection北京大学基础医学院_病理学系
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
GB/T 7714
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.
APA Li, Mengsen.,Li, Hui.,Li, Chaoying.,Zhou, Sheng.,Guo, Liyuan.,...&Li, Gang.(2009).Alpha fetoprotein is a novel protein-binding partner for caspase-3 and blocks the apoptotic signaling pathway in human hepatoma cells.INTERNATIONAL JOURNAL OF CANCER,124(12),2845-2854.
MLA Li, Mengsen,et al."Alpha fetoprotein is a novel protein-binding partner for caspase-3 and blocks the apoptotic signaling pathway in human hepatoma cells".INTERNATIONAL JOURNAL OF CANCER 124.12(2009):2845-2854.
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