A Genetic Screen for Candidate Tumor Suppressors Identifies REST. Export

@article{citeulike:232589, 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.}, address = {Howard Hughes Medical Institute, Department of Genetics, Harvard Partners Center for Genetics and Genomics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115.}, author = {Westbrook, T. F. and Martin, E. S. and Schlabach, M. R. and Leng, Y. and Liang, A. C. and Feng, B. and Zhao, J. J. and Roberts, T. M. and Mandel, G. and Hannon, G. J. and Depinho, R. A. and Chin, L. and Elledge, S. J.}, citeulike-article-id = {232589}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.cell.2005.03.033}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/15960972}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=15960972}, doi = {10.1016/j.cell.2005.03.033}, issn = {0092-8674}, journal = {Cell}, keywords = {cancer, genomics, rnai}, month = {June}, number = {6}, pages = {837--848}, posted-at = {2006-01-19 02:49:23}, priority = {2}, title = {A Genetic Screen for Candidate Tumor Suppressors Identifies REST.}, url = {http://dx.doi.org/10.1016/j.cell.2005.03.033}, volume = {121}, year = {2005} }

TY - JOUR ID - citeulike:232589 L3 - citeulike-article-id:232589 N2 - 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. IS - 6 JF - Cell SN - 0092-8674 AD - Howard Hughes Medical Institute, Department of Genetics, Harvard Partners Center for Genetics and Genomics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115. EP - 848 TI - A Genetic Screen for Candidate Tumor Suppressors Identifies REST. VL - 121 SP - 837 KW - cancer KW - genomics KW - rnai AU - Westbrook, TF AU - Martin, ES AU - Schlabach, MR AU - Leng, Y AU - Liang, AC AU - Feng, B AU - Zhao, JJ AU - Roberts, TM AU - Mandel, G AU - Hannon, GJ AU - Depinho, RA AU - Chin, L AU - Elledge, SJ PY - 2005/06/17/ UR - http://dx.doi.org/10.1016/j.cell.2005.03.033 ER -