Network analysis of oncogenic Ras activation in cancer

被引：87
作者：
Stites, Edward C.
Trampont, Paul C.
Ma, Zhong
Ravichandran, Kodi S. [1 ]
机构：
[1] Univ Virginia, Beirne Carter Ctr Immunol Res, Charlottesville, VA 22908 USA
[2] Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA
[3] Univ Virginia, Med Scientist Training Program, Charlottesville, VA 22908 USA
[4] Univ Virginia, Interdisciplinary Program Biophys, Charlottesville, VA 22908 USA
来源：
SCIENCE | 2007年 / 318卷 / 5849期
关键词：
D O I：
10.1126/science.1144642
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
To investigate the unregulated Ras activation associated with cancer, we developed and validated a mathematical model of Ras signaling. The model-based predictions and associated experiments help explain why only one of two classes of activating Ras point mutations with in vitro transformation potential is commonly found in cancers. Model-based analysis of these mutants uncovered a systems-level process that contributes to total Ras activation in cells. This predicted behavior was supported by experimental observations. We also used the model to identify a strategy in which a drug could cause stronger inhibition on the cancerous Ras network than on the wild-type network. This system-level analysis of the oncogenic Ras network provides new insights and potential therapeutic strategies.
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收藏
页码：463 / 467
页数：5
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