The vulnerable cancer cell(rategy is as follows: A mutated cancer-c...),Health

Date:5/28/2009

rategy is as follows: A mutated cancer-causing gene, or oncogene, causes a cell to grow abnormally. That abnormal growth can lead to the development of a tumor. But oncogenes do not cause cancer by themselves they depend on the activity of other genes. These genes are considered "dependents," in the sense that the cancer cell's survival also depends on the activity of the oncogenes and its dependent genes. Many of these so-called dependent genes are not mutated in cancer cells, but they contribute to abnormal cell growth and cancer. By using RNAi to knock down the expression of individual genes in cells bearing mutations in an oncogene, such as KRAS, researchers can see which gene knock-downs affect cancer cells' viability. Gene dependencies are uncovered in cancer cells that fail to thrive.

Until recently, however, researchers simply did not have the tools to undertake a large-scale, systematic analysis to uncover genetic dependencies in mammalian cells. The discovery of RNAi a little more than a decade ago is making it possible to do genetics in mammalian cells. The cellular machinery involved in RNAi first identifies short segments of suspicious-looking RNA, and then destroys all identical copies of that RNA. The result: None of the protein that the RNA encodes for gets made.

While the natural function of RNAi is to prevent viruses from replicating inside cells and to control endogenous gene expression, scientists discovered they could exploit the process to squelch individual gene products. To do so, they introduce a short segment of RNA that looks like one of the cell's normal genes. The RNA interference machinery grinds into action and shuts down production of the protein made from that gene.

Gilliland's team, which included first authors, Claudia Scholl and Stefan Frhling, as well as HHMI investigator Tyler Jacks at MIT, began their studies about two years ago. The team's interest in leukemias informed their decision to focus on us
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Contact: Jim Keeley keeleyj@hhmi.org 301-215-8858 Howard Hughes Medical Institute Source:Eurekalert

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