对候选瘤抑制剂的基因选识别了REST
Thomas F Westbrook1, Eric S Martin, Michael R Schlabach
1Howard Hughes Medical Institute, Department of Genetics, Harvard Partners Center for Genetics and Genomics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
Cell
|June 18, 2005
概括
研究人员将REST/NRSF确定为一种新的瘤抑制基因. 失去REST通过增加PI(3) K信号来促进癌症,为癌症基因发现提供了新的途径.
科学领域:
- 癌症生物学 癌症生物学
- 分子瘤学分子瘤学
- 遗传学 是一个遗传学.
背景情况:
- 瘤发生涉及复杂的遗传和表观遗传变化.
- 确定驱动恶性转变的关键基因对于癌症研究至关重要.
研究的目的:
- 在人类乳腺上皮细胞中使用RNAi屏幕识别抑制恶性转变的基因.
- 研究REST/NRSF在癌症发展中的作用.
主要方法:
- 基于RNA干扰 (RNAi) 的基因选用于转化抑制剂.
- 对基因改变进行数组比较基因组杂交 (Array-CGH).
- 在结直肠癌细胞中的突变分析.
主要成果:
- 确定已知瘤抑制剂 (TGFBR2,PTEN) 和一种新型抑制剂,REST/NRSF.
- 在结直肠癌中发现了REST删除和转换REST突变.
- 已证明的缺少REST的细胞依赖PI(3) K信号进行转换.
结论:
- 休息功能作为人类瘤抑制剂,以前未被识别.
- 通过PI(3)K通路激活,REST损失有助于癌症.
- 这项研究为发现新的抑制癌症的基因提供了一种方法.
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