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Screening for Sensitivity to Drugs

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Science  17 Jun 2005:
Vol. 308, Issue 5729, pp. 1717
DOI: 10.1126/science.308.5729.1717c

Inappropriate cell death or survival can lead to various diseases, such as neurodegenerative disorders and cancer. MacKeigan et al. performed large-scale screens using short interfering RNAs (siRNAs) transfected into cultured human cell lines to identify kinases and phosphatases involved in cell survival. Seventy-three kinases and 72 phosphatases were identified as contributing positively to cell survival, based on an increase in markers for programmed cell death (apoptosis) when the levels of these proteins were reduced. The phosphatase siRNA library was used to screen for phosphatases involved in cell death induced by cisplatin, Taxol, or etopside; 12 such death-promoting phosphatases were identified. The RNA interference screen was also used to identify kinases that, when downregulated, conferred an increased sensitivity to apoptosis-inducing drugs. For instance, Taxol combined with the siRNA for serum and glucocorticoid-regulated kinase increased cell death as compared with the siRNA or the drug alone. Taken all together, these results may suggestion new combination therapies. — NG

Nat. Cell Biol. 7, 591 (2005).

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