第二个信号由胰岛素样生长因子II在瘤基因诱导的瘤发生过程中提供
G Christofori1, P Naik, D Hanahan
1Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0534.
Nature
|June 2, 1994
概括
转基因小鼠发生胰腺瘤. 胰岛素样生长因子II (IGF-II) 的激活触发了增殖,阻断IGF-II减少了瘤恶性并增加了细胞死亡.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 在胰岛素基因调节下,表达猿人病毒-40大T抗原 (Tag) 的转基因小鼠作为瘤发生模型.
- 标签的初始小岛表达不会导致异常增殖.
研究的目的:
- 在转基因小鼠中研究驱动小岛瘤形成的分子机制.
- 确定胰岛素样生长因子II (IGF-II) 在增殖开关中的作用.
主要方法:
- 使用转基因小鼠模型,在胰腺小岛中表达Tag.
- 使用反感性寡核酸转染来抑制IGF-II信使RNA.
- 在IGF-II基因被破坏的小鼠中分析瘤发育,恶性瘤和亡.
主要成果:
- IGF-II的焦点激活与小岛的初始繁殖开关相关.
- 抑制IGF-II信使RNA可以在体外减少瘤细胞的增殖.
- 缺乏功能性IGF-II的小鼠表现出瘤恶性减少和亡增加.
结论:
- 瘤蛋白 (Tag) 和生长/生存因子 (IGF-II) 都是导致岛屿瘤的超增殖所必需的.
- 在这个模型中,IGF-II在瘤发生的进展中起着至关重要的作用.
- 向IGF-II可能为胰腺瘤提供治疗策略.
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