A genetic screen for candidate tumor suppressors identifies REST

Westbrook, T. F., Martin, E. S., Schlabach, M. R., Leng, Y. M., Liang, A. C., Feng, B., Zhao, J. J., Roberts, T. M., Mandel, G., Hannon, G. J., DePinho, R. A., Chin, L., Elledge, S. J. (June 2005) A genetic screen for candidate tumor suppressors identifies REST. Cell, 121 (6). pp. 837-848. ISSN 0092-8674

URL: https://www.ncbi.nlm.nih.gov/pubmed/15960972
DOI: 10.1016/j.cell.2005.03.033

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.

Item Type: Paper
Uncontrolled Keywords: Mammary epithelial cells TGF beta HUMAN CANCER TRANSFORMATION Ras RAS EXPRESSION PATHWAY Adenocancer proliferation REQUIREMENTS
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > annotation > gene expression profiling annotation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNAi
diseases & disorders > cancer > cancer types > breast cancer
CSHL Authors:
Communities: CSHL labs > Hannon lab
Depositing User: CSHL Librarian
Date: June 2005
Date Deposited: 21 Dec 2011 16:46
Last Modified: 02 Dec 2016 17:16
Related URLs:
URI: http://repository.cshl.edu/id/eprint/22734

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