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学科主题: 基础医学
题名:
Adenovirus-expressed human hyperplasia suppressor gene induces apoptosis in cancer cells
作者: Wu, Lina1; Li, Zhixin1; Zhang, Yingmei1; Zhang, Pei1; Zhu, Xiaohui1; Huang, Jing1; Ma, Teng1; Lu, Tian1; Song, Quansheng1; Li, Qian2,3; Guo, Yanhong2,3; Tang, Jian2,3; Ma, Dalong1; Chen, Kuang-Hueih2,3; Qiu, Xiaoyan1
刊名: MOLECULAR CANCER THERAPEUTICS
发表日期: 2008
DOI: 10.1158/1535-7163.MCT-07-0382
卷: 7, 期:1, 页:222-232
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]: MITOCHONDRIAL FUSION ; BAX ; PROTEIN ; ACTIVATION ; MORPHOLOGY ; MITOFUSINS ; GTPASE ; MFN2 ; P53
英文摘要:

Hyperplasia suppressor gene (HSG), also called human mitofusin 2, is a novel gene that markedly suppresses the cell proliferation of hyperproliferative vascular smooth muscle cells from spontaneously hypertensive rat arteries. This gene encodes a mitochondrial membrane protein that participates in mitochondrial fusion and contributes to the maintenance and operation of the mitochondrial network. In this report, we showed that an adenovirus vector encoding human HSG (Ad5-hHSG) had an antitumor activity in a wide range of cancer cell lines. We further focused on the lung cancer cell line, A549 and the colon cancer cell line HT-29 and then observed that Ad5-hHSG induced apoptosis both in vitro and in vivo. Confocal laser scanning microscopy and electron microscopy revealed that cells infected with Ad5-hHSG formed dose-dependent perinuclear clusters of fused mitochondria. Adenovirus-mediated hHSG overexpression induced apoptosis, cell cycle arrest, mitochondrial membrane potential (Delta Psi m) reduction and release of cytochrome c, caspase-3 activation, and cleavage of PARP in vitro. Overexpression of hHSG also significantly suppressed the growth of subcutaneous tumors in nude mice both ex vivo and in vivo. In addition, Ad5-hHSG increased the sensitivity of these cell lines to two chemotherapeutic agents, VP16 and CHX, and radiation. These results suggest that Ad5-hHSG may serve as an effective therapeutic drug against tumors.

语种: 英语
WOS记录号: WOS:000252580900023
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/54632
Appears in Collections:基础医学院_北京大学人类疾病基因研究中心_期刊论文

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作者单位: 1.Peking Univ, Ctr Human Dis Genom, Hlth Sci Ctr, Beijing 100083, Peoples R China
2.Peking Univ, Inst Cardiovasc Sci, Beijing 100871, Peoples R China
3.Peking Univ, Inst Mol Med, Beijing 100871, Peoples R China

Recommended Citation:
Wu, Lina,Li, Zhixin,Zhang, Yingmei,et al. Adenovirus-expressed human hyperplasia suppressor gene induces apoptosis in cancer cells[J]. MOLECULAR CANCER THERAPEUTICS,2008,7(1):222-232.
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