Profiling essential genes in human mammary cells by multiplex RNAi screening

Silva, J. M., Marran, K., Parker, J. S., Silva, J., Golding, M., Schlabach, M. R., Elledge, S. J., Hannon, G. J., Chang, K. (February 2008) Profiling essential genes in human mammary cells by multiplex RNAi screening. Science, 319 (5863). pp. 617-20.

URL: http://www.ncbi.nlm.nih.gov/pubmed/18239125
DOI: 10.1126/science.1149200

Abstract

By virtue of their accumulated genetic alterations, tumor cells may acquire vulnerabilities that create opportunities for therapeutic intervention. We have devised a massively parallel strategy for screening short hairpin RNA (shRNA) collections for stable loss-of-function phenotypes. We assayed from 6000 to 20,000 shRNAs simultaneously to identify genes important for the proliferation and survival of five cell lines derived from human mammary tissue. Lethal shRNAs common to these cell lines targeted many known cell-cycle regulatory networks. Cell line-specific sensitivities to suppression of protein complexes and biological pathways also emerged, and these could be validated by RNA interference (RNAi) and pharmacologically. These studies establish a practical platform for genome-scale screening of complex phenotypes in mammalian cells and demonstrate that RNAi can be used to expose genotype-specific sensitivities.

Item Type: Paper
Uncontrolled Keywords: Breast/*cytology/*metabolism Breast Neoplasms/*genetics/pathology Cell Line Cell Line, Tumor *Cell Proliferation *Cell Survival Gene Expression Profiling *Genes, Essential Genomics Humans Metabolic Networks and Pathways/*genetics Oligonucleotide Array Sequence Analysis Phenotype *RNA Interference RNA, Small Interfering
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
Investigative techniques and equipment
Investigative techniques and equipment > RNAI
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
organs, tissues, organelles, cell types and functions > tissues types and functions > mammary gland
organs, tissues, organelles, cell types and functions
organs, tissues, organelles, cell types and functions > tissues types and functions
CSHL Authors:
Communities: CSHL labs > Hannon lab
Depositing User: Matt Covey
Date: 1 February 2008
Date Deposited: 25 Feb 2013 21:30
Last Modified: 25 Feb 2013 21:30
PMCID: PMC2981861
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27596

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