Use of retrovirus expression of interfering RNA to determine the contribution of activated K-ras and ras effector expression to human tumor cell growth

被引:19
作者
Baines, Antonio T. [1 ]
Lim, Kian-Huat
Shields, Janiel M.
Lambert, John M.
Counter, Christopher M.
Der, Channing J.
Cox, Adrienne D.
机构
[1] Univ N Carolina, Dept Radiat Oncol, Chapel Hill, NC 27599 USA
[2] Univ N Carolina, Dept Dermatol, Chapel Hill, NC USA
[3] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27515 USA
来源
REGULATORS AND EFFECTORS OF SMALL GTPASES: RAS FAMILY | 2006年 / 407卷
关键词
D O I
10.1016/S0076-6879(05)07045-X
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Cancer is a multistep genetic process that includes mutational activation of oncogenes and inactivation of tumor suppressor genes. The Ras oncogenes are the most frequently mutated oncogenes in human cancers (30%), with a high frequency associated with cancers of the lung, colon, and pancreas. Mutational activation of Ras is commonly an early event in the development of these cancers. Thus, whether mutated Ras is required for tumor maintenance and what aspects of the complex malignant phenotype might be promoted by mutated Ras are issues that remain unresolved for these and other human cancers. The recent development of interfering RNA to selectively impair expression of mutated Ras provides a powerful approach to begin to resolve these issues. In this chapter, we describe the use of retrovirus-based RNA interference approaches to study the functions of Ras and Ras effectors (Raf, RalA, RalB, and Tiam1) in the growth of pancreatic carcinoma and other human tumor cell lines. Finally, we also compare the use of constitutive and inducible shRNA expression vectors for analyses of mutant Ras function.
引用
收藏
页码:556 / +
页数:22
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