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CSHL study shows that some malignant tumors can be shut down after all
Date:11/9/2009

Cold Spring Harbor, N.Y. Oncologists have had their hands tied because more than half of all human cancers have mutations that disable a protein called p53. As a critical anti-cancer watchdog, p53 masterminds several cancer-fighting operations within cells. When cells lose p53, tumors grow aggressively and often cannot be treated.

These tumors might be tough, but they're not invincible, suggests a new study from Cold Spring Harbor Laboratory (CSHL). The chink in the tumors' armor, according to CSHL Associate Professor Alea Mills, Ph.D., is a protein called TAp63, an older sibling of p53 that's usually intact and not mutated in most cancers.

Mills and her team have succeeded in shutting off the growth of tumors in which p53 is missing by turning up the production of TAp63 proteins, which make up one class of proteins produced by the p63 gene. TAp63 completely blocked tumor initiation, the team found, by inducing senescence, a state of growth arrest in which tumor cells are still metabolically alive but fail to divide. More importantly, turning up the levels of TAp63 in cells that did not have p53 blocked the progression of established tumors in mice.

"We were very excited to see that TAp63 shuts down cancer completely independently of p53," says Mills. "This means that we now have a way of attacking cancers that have damaged p53, which are very difficult to treat in the clinic." The study, funded by a Research Scholar Award from the American Cancer Society, appears online ahead of print on November 8th in Nature Cell Biology.

TAp63 protects from cancer

"p63 is a double-edged sword," says Mills, who discovered it when she was a postdoctoral researcher almost a decade ago. Of the six different proteins that are produced from the p63 gene, three promote activities that could lead to cancer. The remaining three, which are TAp63 versions, do the opposite: prevent cancer by triggering senescencea process th
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Contact: Hema Bashyam
bashyam@cshl.edu
516-367-6822
Cold Spring Harbor Laboratory
Source:Eurekalert

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