女科学家《Nature》新增致癌基因

【字体: 时间:2009年07月02日 来源:生物通

编辑推荐:

  生物通报道,哈佛大学医学院Brigham and Women’s Hospital,哈佛医学院系统生物学系,哈佛癌症研究中心,Dana-Farber癌症研究所的研究人员在最新一期的《Nature》上发表研究进展GOLPH3 modulates mTOR signalling and rapamycin sensitivity in cancer。

  

生物通报道,哈佛大学医学院Brigham and Women’s Hospital,哈佛医学院系统生物学系,哈佛癌症研究中心,Dana-Farber癌症研究所的研究人员在最新一期的《Nature》上发表研究进展GOLPH3 modulates mTOR signalling and rapamycin sensitivity in cancer

 

文章通讯作者是来自哈佛医学院的Lynda Chin教授,主要从事癌症分子遗传学与生物学方面的研究。

 

对多种固体癌分析发现,癌细胞的基因组上的5p13区域常发生拷贝数突变,包括,肺癌(56%),卵巢癌(38%),乳腺癌(32%),前列腺癌(37%)以及黑色素瘤(32%)。

 

Lynda Chin等人对基因组的该区域进行系统性分析发现:Golgi蛋白GOLPH3可能是癌症发生的一个关键因素。进一步体外和体内实验发现,GOLPH3是一个致癌基因。GOLPH3定位于Golgi网络上,并能与retromerTOR信号通路上的靶位)相互作用。

 

遗传技术和生物学技术分析表明,GOLPH3是一个全新的致癌基因,能促进人类癌细胞增殖,同时还能调节癌细胞对rapamycin的敏感性。GOLPH3可能是癌症药物的有利靶位。

(生物通 小茜)

生物通推荐原文检索:

GOLPH3 modulates mTOR signalling and rapamycin sensitivity in cancer

 

Kenneth L. Scott1,9, Omar Kabbarah1,9, Mei-Chih Liang1,4, Elena Ivanova2, Valsamo Anagnostou5, Joyce Wu1, Sabin Dhakal1, Min Wu1, Shujuan Chen1, Tamar Feinberg1, Joseph Huang1, Abdel Saci6, Hans R. Widlund3,7, David E. Fisher3,8, Yonghong Xiao2, David L. Rimm5, Alexei Protopopov2, Kwok-Kin Wong1,4 & Lynda Chin1,2,7

Department of Medical Oncology,

Belfer Institute for Applied Cancer Science,

Department of Pediatric Oncology, Dana-Farber Cancer Institute,

Ludwig Center at Dana-Farber/Harvard Cancer Center, Boston, Massachusetts 02115, USA

Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520, USA

Department of Systems Biology, Harvard Medical School,

Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA

Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA

Abstract

Genome-wide copy number analyses of human cancers identified a frequent 5p13 amplification in several solid tumour types, including lung (56%), ovarian (38%), breast (32%), prostate (37%) and melanoma (32%). Here, using integrative analysis of a genomic profile of the region, we identify a Golgi protein, GOLPH3, as a candidate targeted for amplification. Gain- and loss-of-function studies in vitro and in vivo validated GOLPH3 as a potent oncogene. Physically, GOLPH3 localizes to the trans-Golgi network and interacts with components of the retromer complex, which in yeast has been linked to target of rapamycin (TOR) signalling. Mechanistically, GOLPH3 regulates cell size, enhances growth-factor-induced mTOR (also known as FRAP1) signalling in human cancer cells, and alters the response to an mTOR inhibitor in vivo. Thus, genomic and genetic, biological, functional and biochemical data in yeast and humans establishes GOLPH3 as a new oncogene that is commonly targeted for amplification in human cancer, and is capable of modulating the response to rapamycin, a cancer drug in clinical use.

相关新闻
生物通微信公众号
微信
新浪微博
  • 搜索
  • 国际
  • 国内
  • 人物
  • 产业
  • 热点
  • 科普
  • 急聘职位
  • 高薪职位

知名企业招聘

热点排行

    今日动态 | 生物通商城 | 人才市场 | 核心刊物 | 特价专栏 | 仪器云展台 | 免费试用 | 今日视角 | 新技术专栏 | 技术讲座 | 技术期刊 | 会展中心 | 中国科学人 | 正牌代理商

    版权所有 生物通

    Copyright© eBiotrade.com, All Rights Reserved

    联系信箱:

    粤ICP备09063491号