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Cancer Cell. 2009 Oct 6;16(4):324-35. doi: 10.1016/j.ccr.2009.08.015.

Functional identification of tumor-suppressor genes through an in vivo RNA interference screen in a mouse lymphoma model.

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  • 1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.

Abstract

Short hairpin RNAs (shRNAs) capable of stably suppressing gene function by RNA interference (RNAi) can mimic tumor-suppressor-gene loss in mice. By selecting for shRNAs capable of accelerating lymphomagenesis in a well-characterized mouse lymphoma model, we identified over ten candidate tumor suppressors, including Sfrp1, Numb, Mek1, and Angiopoietin 2. Several components of the DNA damage response machinery were also identified, including Rad17, which acts as a haploinsufficient tumor suppressor that responds to oncogenic stress and whose loss is associated with poor prognosis in human patients. Our results emphasize the utility of in vivo RNAi screens, identify and validate a diverse set of tumor suppressors, and have therapeutic implications.

PMID:
19800577
[PubMed - indexed for MEDLINE]
PMCID:
PMC2829755
Free PMC Article

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