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Keeping cancer in check

(Philadelphia, PA) Researchers at the University of Pennsylvania School of Medicine have identified in normal cells that a common metabolic enzyme, which acts as a rheostat of cellular conditions, also controls cell replication. This control is managed through p53, the much-studied protein implicated in many types of cancer. The discovery of the interaction between these two molecules may lead to new ways to fight cancer. First author Russell G. Jones, PhD, a postdoctoral fellow in the laboratory of senior author Craig Thompson, MD, at the Abramson Family Cancer Research Institute at Penn, and colleagues describe their findings in the most recent issue of Molecular Cell.

This work tests the novel notion that cancer cells co-opt cellular pathways that govern metabolism in order to proliferate beyond a cell's normal means. Cancer cells have, by definition, a high metabolic rate and consume glucose at a high rate. One of the fundamental questions being tested in the Thompson lab is the importance of metabolism in cancer and investigating how cancer cells differ from normal cells, allowing them to survive and replicate. (Thompson is the Chair of Penn's Department of Cancer Biology and Scientific Director of the Abramson Family Cancer Research Institute.)

"We think that the enzyme interprets the energetic environment of the cell," explains Jones. "It senses the stress a cell sees such as low oxygen, low glucose, or the presence of free radicals and, from this, can induce a check on replication through p53, acting in effect as a tumor-suppressor."

For this study, the investigators looked at noncancerous mouse cells called fibroblasts to see how normal cells work and what they do physiologically when faced with an environmental challenge: in this case, low glucose levels, explains Jones.

When the enzyme called AMP-activated protein kinase (AMPK) is turned on, it prevents cells from replicating. It acts as a sensor to detect energy lev
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
4-May-2005


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