Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

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 and Kenneth Chang
Science
New Series, Vol. 319, No. 5863 (Feb. 1, 2008), pp. 617-620
Stable URL: http://www.jstor.org/stable/20053257
Page Count: 4
  • More info
  • Cite this Item
Preview not available
Preview not available

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.

Page Thumbnails

  • Thumbnail: Page 
617
    617
  • Thumbnail: Page 
618
    618
  • Thumbnail: Page 
619
    619
  • Thumbnail: Page 
620
    620