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学科主题基础医学
Upregulation of LAPTM4B-35 Promotes Malignant Transformation and Tumorigenesis in L02 Human Liver Cell Line
Li, Li2; Shan, Yi2; Yang, Hua2; Zhang, Sha2; Lin, Ming2; Zhu, Ping3; Chen, Xin-Yu3; Yi, Jing3; Mcnutt, Michael A.1; Shao, Gen-Ze2; Zhou, Rou-Li1,2
关键词LAPTM4B-35 tumorigenesis apoptosis
刊名ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY
2011-07-01
DOI10.1002/ar.21421
294期:7页:1135-1142
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Anatomy & Morphology
研究领域[WOS]Anatomy & Morphology
关键词[WOS]HEPATOCELLULAR-CARCINOMA ; CANCER ; OVEREXPRESSION ; DEATH ; EPIDEMIOLOGY ; PROGRESSION ; EXPRESSION ; APOPTOSIS ; CASPASE-3 ; SURVIVAL
英文摘要

Hepatocellular carcinoma (HCC) is one of the most frequent malignant neoplasms worldwide and is the second leading cause of cancer death in China. We have previously demonstrated that LAPTM4B-35, encoded by lysosomal protein transmembrane 4 beta gene, is overexpressed in over 80% of HCCs and is a novel-independent prognostic factor for metastasis, recurrence, and postoperative survival in HCC. In this study, we investigated the role of LAPTM4B-35 in malignant transformation and tumorigenesis using L02 cells, a cell line originated from human normal liver cells. Our data show that replication-deficient adenovirus vector-mediated upregulation of LAPTM4B-35 promotes anchorage-independent proliferation and resistance to adriamycin-induced apoptosis. Study of the underlying mechanisms demonstrated alterations of molecular events involved in these processes, which included the activation of phosphoinositide 3-kinases (PI3K)/serine/threonine protein kinase B (PKB/AKT)/bcl-xL/bcl-2-associated death promoter homolog (Bad) signaling pathway, inhibition of caspase-3 activation, upregulation of Bcl-2, and down-regulation of Bax. In addition, upregulation of LAPTM4B-35 in L02 cells resulted in tumorigenesis in 100% (6/6) of inoculated nude mice and accelerated the death of mice with xenografts in vivo. In conclusion, LAPTM4B-35 promotes malignant transformation and tumorigenesis in human liver L02 cell line through promotion of deregulated proliferation and inhibition of apoptosis. These findings suggest that overexpression of LAPTM4B-35 may play a critical role in hepatocarcinogenesis and therefore, may be a therapeutic target for HCC. Anat Rec, 294:1135-1142, 2011. (C) 2011Wiley-Liss, Inc.

语种英语
WOS记录号WOS:000291951800006
项目编号2006AA02A305 ; ZH100010502
资助机构National High Technology R& ; D Program (863 Program) ; Ministry of Education P.R.C. ; Beijing Municipal Education Commission
引用统计
被引频次:11[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/56856
专题北京大学基础医学院_病理学系
北京大学医学部管理机构_计划财务处
北京大学基础医学院
作者单位1.Peking Univ, Sch Basic Med Sci, Dept Pathol, Beijing 100191, Peoples R China
2.Peking Univ, Dept Cell Biol, Hlth Sci Ctr, Beijing 100191, Peoples R China
3.Shanghai Jiao Tong Univ, Sch Med, Dept Cell Biol, Shanghai 200030, Peoples R China
推荐引用方式
GB/T 7714
Li, Li,Shan, Yi,Yang, Hua,et al. Upregulation of LAPTM4B-35 Promotes Malignant Transformation and Tumorigenesis in L02 Human Liver Cell Line[J]. ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY,2011,294(7):1135-1142.
APA Li, Li.,Shan, Yi.,Yang, Hua.,Zhang, Sha.,Lin, Ming.,...&Zhou, Rou-Li.(2011).Upregulation of LAPTM4B-35 Promotes Malignant Transformation and Tumorigenesis in L02 Human Liver Cell Line.ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY,294(7),1135-1142.
MLA Li, Li,et al."Upregulation of LAPTM4B-35 Promotes Malignant Transformation and Tumorigenesis in L02 Human Liver Cell Line".ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY 294.7(2011):1135-1142.
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