Profiling essential genes in human mammary cells by multiplex RNAi screening

Jose M. Silva, Krista Marran, Joel S. Parker, Javier Silva, Michael Golding, Michael R. Schlabach, Stephen J. Elledge, Gregory J. Hannon, Kenneth Chang

Research output: Contribution to journalArticlepeer-review

256 Scopus citations

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.

Original languageEnglish
Pages (from-to)617-620
Number of pages4
JournalScience
Volume319
Issue number5863
DOIs
StatePublished - 1 Feb 2008
Externally publishedYes

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