Profiling Essential Genes in Human Mammary Cells by Multiplex RNAi Screening Academic Article uri icon


  • 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.

altmetric score

  • 10

author list (cited authors)

  • Silva, J. M., Marran, K., Parker, J. S., Silva, J., Golding, M., Schlabach, M. R., ... Chang, K.

citation count

  • 255

complete list of authors

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

publication date

  • February 2008