Combined Gene Expression Profiling and RNAi Screen... [Cancer Res. 2011] - PubMed result

Cancer Res. 2011 Jun 3. [Epub ahead of print]
Combined Gene Expression Profiling and RNAi Screening in Clear Cell Renal Cell Carcinoma Identify PLK1 and Other Therapeutic Kinase Targets.
Ding Y, Huang D, Zhang Z, Smith J, Petillo D, Looyenga BD, Feenstra K, Mackeigan JP, Furge KA, Teh BT.
Source
National Center for Environmental Health, Centers for Disease Control and Prevention.


Abstract
In recent years, several molecularly targeted therapies have been approved for clear cell renal cell carcinoma (ccRCC), a highly aggressive cancer. Although these therapies significantly extend overall survival, nearly all patients with advanced ccRCC eventually succumb to the disease. To identify other molecular targets, we profiled gene expression in 90 ccRCC patient specimens for which tumor grade information was available. Gene set enrichment analysis indicated that cell cycle-related genes, in particular Polo-like kinase 1 (PLK1), were associated with disease aggressiveness. We also performed RNAi screening to identify kinases and phosphatases that when inhibited could prevent cell proliferation. As expected, RNAi-mediated knockdown of PLK1 and other cell cycle kinases was sufficient to suppress ccRCC cell proliferation. The association of PLK1 in both disease aggression and in vitro growth prompted us to examine the effects of a small-molecule inhibitor of PLK1, BI 2536, in ccRCC cell lines. BI 2536 inhibited the proliferation of ccRCC cell lines at concentrations required to inhibit PLK1 kinase activity, and sustained inhibition of PLK1 by BI 2536 led to dramatic regression of ccRCC xenograft tumors in vivo. Taken together, these findings highlight PLK1 as a rational therapeutic target for ccRCC.

PMID:21642374[PubMed - as supplied by publisher]
Combined Gene Expression Profiling and RNAi Screen... [Cancer Res. 2011] - PubMed result