@article{26014e7351f746a39b259eea534fe748,
title = "A genetic screen for candidate tumor suppressors identifies REST",
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.",
author = "Westbrook, {Thomas F.} and Martin, {Eric S.} and Schlabach, {Michael R.} and Yumei Leng and Liang, {Anthony C.} and Bin Feng and Zhao, {Jean J.} and Roberts, {Thomas M.} and Gail Mandel and Hannon, {Gregory J.} and DePinho, {Ronald A.} and Lynda Chin and Elledge, {Stephen J.}",
note = "Funding Information: We are grateful to Joan Massague, Dennis McCance, Barry Thrash, and Xiao-Jing Wang for the gift of reagents. We recognize the Harvard Partners Genome Center at HPCGG for the sequencing of human tumor DNA. We thank Mamie Li, Zhenming Zhou, and Nancy Ryan for technical support and Frank Stegmeier, Guang Hu, Robert McDonald, Jennifer Hackett, and Don Nguyen for critical reading of the manuscript. We are also grateful to Joan Massague, Robert Darnell, and Matthew Meyerson and members of the Elledge and Hannon laboratories for helpful discussions. T.F.W. is a fellow of the Susan G. Komen Foundation and is supported by grant PDF0403175. This work was supported by grants from NCI 5T32CA09361 (E.S.M.), NCI MMHCC U01 CA084313 (R.A.D.), RO1CA93947 and RO1CA99041 (L.C.), 5 P50 CA090381-03 (J.J.Z.), and 5 P01 CA89021-04 and D.O.D.17-02-1-0692 (T.M.R.); grants from the NIH and DOD (G.J.H.); and a U.S. Army Innovator Award (W81XWH0410197) (to S.J.E.). R.A.D. is an American Cancer Society Research Professor. G.M. and S.J.E. are investigators with the Howard Hughes Medical Institute. ",
year = "2005",
month = jun,
day = "17",
doi = "10.1016/j.cell.2005.03.033",
language = "English (US)",
volume = "121",
pages = "837--848",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "6",
}