Journal
SCIENCE
Volume 319, Issue 5863, Pages 620-624Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1149200
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Funding
- Howard Hughes Medical Institute Funding Source: Medline
- NCI NIH HHS [P01 CA013106-36, P01 CA013106, P01 CA013106-37, T32 CA009216, T32CA09216] Funding Source: Medline
- NIA NIH HHS [R01 AG011085] Funding Source: Medline
- NINDS NIH HHS [F31 NS054507-01, F31 NS054507] Funding Source: Medline
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Retroviral short hairpin RNA (shRNA) - mediated genetic screens in mammalian cells are powerful tools for discovering loss- of- function phenotypes. We describe a highly parallel multiplex methodology for screening large pools of shRNAs using half- hairpin barcodes for microarray deconvolution. We carried out dropout screens for shRNAs that affect cell proliferation and viability in cancer cells and normal cells. We identified many shRNAs to be antiproliferative that target core cellular processes, such as the cell cycle and protein translation, in all cells examined. Moreover, we identified genes that are selectively required for proliferation and survival in different cell lines. Our platform enables rapid and cost- effective genome-wide screens to identify cancer proliferation and survival genes for target discovery. Such efforts are complementary to the Cancer Genome Atlas and provide an alternative functional view of cancer cells.
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