"There are a number of genes that can cause cancer, the so-called oncogenes, but Pokemon is unique in that it is needed for other oncogenes to cause cancer." said MSKCC cancer geneticist Pier Paolo Pandolfi, MD, PhD, the senior author of the study. "More important, because the Pokemon protein plays such a crucial role in the formation of cancer, it could prove to be an effective target for new drug therapies."
Pokemon works by controlling the pathways that are required to transform normal cells to cancerous ones. The researchers found that when they "knocked out" the Pokemon gene in mice, that transformation was blocked and cells do not become cancerous. (Knocking out a gene means inactivating it through genetic engineering.) A drug that could block the protein's function in the same way could be a powerful anticancer agent.
"Pokemon is a main switch in the molecular network that leads toward cancer," Dr. Pandolfi added. "If we could turn Pokemon off, it may block this oncogenic circuitry and stall the malignant process."
The investigators confirmed Pokemon's cancer-causing role by inserting the oncogene into mice. Pokemon does its damage by repressing the function of other proteins, including a tumor suppressor called ARF. The mice developed aggressive, fatal forms of lymphoma. In further work, using a technique called tissue micro arrays to study tumor samples from people with many types of cancer, they confirmed that Pokemon is present in very high levels in certain types of B-cell and T-cell lymphoma
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Contact: Joanne Nicholas
nicholaj@mskcc.org
212-639-3573
Memorial Sloan-Kettering Cancer Center
19-Jan-2005