通过功能基因组学发现癌症扩散基因
Michael R Schlabach1, Ji Luo, Nicole L Solimini
1Howard Hughes Medical Institute and Department of Genetics, Center for Genetics and Genomics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Science (New York, N.Y.)
|February 2, 2008
概括
这项研究引入了一种使用短毛RNA (shRNA) 进行基因选的新方法,以找到对癌细胞生长和存活至关重要的基因. 该平台可实现潜在的癌症药物标的经济高效的全基因组识别.
科学领域:
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 逆转录病毒短毛针RNA (shRNA) 介导的基因选对于识别哺乳动物细胞中的功能丧失表型至关重要.
- 发现调节细胞增殖和活力的基因对于理解癌症生物学和开发向疗法至关重要.
研究的目的:
- 开发和验证使用半头针条形码进行shRNA查的高通量,多重复合方法.
- 鉴定癌细胞和正常细胞增殖和存活所必需的基因.
- 在不同细胞系中发现有选择性地需要扩散和生存的基因.
主要方法:
- 采用了多重shRNA选方法,使用半头针条形码进行微阵列解卷.
- 进行了脱学查,以确定影响细胞增殖和活力的shRNAs.
- 将该方法应用于癌症和正常细胞系进行比较分析.
主要成果:
- 确定了许多向细胞核心过程 (细胞循环,蛋白质翻译) 的shRNA,它们在所有细胞类型中具有抗增殖作用.
- 发现了在特定癌症细胞系中选择性地增殖和生存所需的基因.
- 展示了该平台的快速和成本效益高的全基因组查能力.
结论:
- 开发的shRNA查平台为识别癌症中必不可少的基因提供了一个强大的工具.
- 这种方法促进了针对抗癌药物开发的快速和经济有效的目标发现.
- 这些发现提供了一个功能性基因组视角,可以补充诸如癌症基因组图谱之类的倡议.
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Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
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