GenomeRNAi - a database for RNAi phenotypes and reagents
TitleScreen TitleAssayBiomodelSpecies
A genetic screen for candidate tumor suppressors identifies REST. Westbrook et al. (2005) Tumor suppressor Cell viabilityHMECs (mammary epithelial cells)H. sapiens

Abstract

Tumorigenesis is a multistep process characterized by a myriad of genetic and epigenetic alterations. Identifying the causal perturbations that confer malignant transformation is a central goal in cancer biology. Here we report an RNAi-based genetic screen for genes that suppress transformation of human mammary epithelial cells. We identified genes previously implicated in proliferative control and epithelial cell function including two established tumor suppressors, TGFBR2 and PTEN. In addition, we uncovered a previously unrecognized tumor suppressor role for REST/NRSF, a transcriptional repressor of neuronal gene expression. Array-CGH analysis identified REST as a frequent target of deletion in colorectal cancer. Furthermore, we detect a frameshift mutation of the REST gene in colorectal cancer cells that encodes a dominantly acting truncation capable of transforming epithelial cells. Cells lacking REST exhibit increased PI(3)K signaling and are dependent upon this pathway for their transformed phenotype. These results implicate REST as a human tumor suppressor and provide a novel approach to identifying candidate genes that suppress the development of human cancer.

Screen details


Stable Id: GR00118-A-0
Screen title: Tumor suppressor
Assay: Cell viability
Method: Micoarray hybridization
Scope:
Screen type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: HMECs (mammary epithelial cells)
Library: , shRNA-mir (G. Hannon)
Reagent type: shRNA
Score type: np
Cutoff: np
Notes: