创建具有定义遗传元素的人类瘤细胞
W C Hahn1, C M Counter, A S Lundberg
1Department of Biology, Massachusetts Institute of Technology, Whitehead Institute for Biomedical Research, Cambridge 02142, USA.
Nature
|August 10, 1999
概括
创造人类瘤细胞是一项挑战. 科学家们发现,将端粒酶 (hTERT) 与两个瘤基因结合,直接将正常人体细胞转化为瘤细胞,为癌症发展提供了新的见解.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 恶性转变涉及遗传突变取代正常细胞增殖控制.
- 动物细胞很容易通过瘤基因转化,但人类细胞抵制瘤性转化.
- 之前的人类瘤细胞的创造需要永生化剂或病毒基因组.
研究的目的:
- 研究一种用于正常人体细胞直接致瘤转换的新方法.
- 为了确定特定的瘤基因和端粒酶是否可以诱导人类瘤形成.
- 阐明人类与动物细胞转化的根本差异.
主要方法:
- 端粒酶催化子单元 (hTERT) 的异位表达.
- 猿人病毒40大Tcoprotein和一个致癌H-ras等位基因的同时表达.
- 使用正常的人类上皮细胞和纤维细胞.
主要成果:
- 实现了人类细胞的直接瘤性转化.
- 结合hTERT,大Tcoprotein和瘤性H-ras是有效的.
- 这种方法绕过了对化学/物理剂或自发不朽化的需求.
结论:
- 通过大T,瘤性ras和端粒酶调节的途径的破坏足以产生人类瘤细胞.
- 突出了人类和动物细胞转化机制的关键差异.
- 为研究人类瘤发生提供了一个新的模型.
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