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Cell growth and death controlled by single pathway in lymphoma cancer model

New research at Rockefeller University, published this week in the online edition of the Proceedings of the National Academy of Sciences, helps explain why some people do not respond to chemotherapy and offers a possible solution.

The cell culture study shows that in a type of lymphoma, molecules involved in the NF-kappa B (NF-kB) signaling pathway -- responsible for pushing cells to grow uncontrollably -- also control the function of the p53 tumor suppressor protein whose function is demolishing those harmful cells. The same interactions could characterize other cancer types, the researchers say.

Most chemotherapy target what was thought to be a discrete "pathway" responsible for cell destruction, such as the p53 protein, but if these proteins are managed -- even protected -- by other key cancer-promoting molecules, the chemotherapy will not work.

Instead, the researchers say it may be possible to target one or both of the genes they found that link both molecular pathways, like intersections joining two highways together in different spots.

"Now that we know the proliferation pathway can jam the p53 suicide pathway, we might be able to block specific sections of those pathways," says the lead researcher, Archontoula Stoffel, Ph.D., a research assistant professor at Rockefeller University.

Blocking only selected pieces of these pathways will be important, Stoffel says, because the NF-kappa B pathway plays a vital role in the body's normal immune and inflammatory responses, although it is also linked to a growing list of cancers. "It is not possible to shut down NF-kB without causing systemic problems, so we need to find out how to disarm its carcinogenic properties down the signaling pathway, while maintaining its useful functions," she says. "This study may help."

The study also is important because it presents the first molecular description of a cancer caused by bacteria, and thus "represents a model system of ho
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Contact: Joseph Bonner
bonnerj@rockefeller.edu
212-327-8998
Rockefeller University
31-May-2004


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