Powerful Anti-Cancer Agent?

"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 Dr. Pandolfi, the senior author of the study.

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 did 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 Linked to Aggressive Tumors

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, the researchers confirmed that Pokemon is present in very high levels in certain types of B-cell and T-cell lymphomas. They also found that tumors with high levels of Pokemon protein were much more likely to be aggressive.

"Pokemon is a member of a family of proteins that are known to be transcription factors and are mutated in human cancer," said Takahiro Maeda, MD, PhD, a postdoctoral research fellow in Dr. Pandolfi's laboratory who was the paper's first author. "It is likely that the protein plays a role in solid tumors as well, and we now have means to specifically interfere with the activity of these transcription factors."