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Jefferson scientists identify protein key to breast cancer spread, potential new drug target

(PHILADELPHIA) Researchers at the Kimmel Cancer Center at Jefferson have identified a protein that they say is key to helping a quarter of all breast cancers spread. The finding, reported online the week of April 9, 2007 in the journal Proceedings of the National Academy of Sciences, could be a potential target for new drugs aimed at stopping or slowing the growth and progression of breast cancer.

Kimmel Cancer Center director Richard Pestell, M.D., Ph.D., professor and chair of cancer biology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, and colleagues genetically engineered mice to lack the protein Akt1, which normally plays a role in keeping cells alive by interfering with programmed cell death. Breast and other cancers make an overabundance of the protein, and its thought to potentially affect survival of breast and other cancer cells as well.

To test that hypothesis, Dr. Pestell and his team bred the mice missing the gene for Akt1 with other mice that overexpressed the HER2-neu (ErbB2) oncogene, which leads to approximately 25 percent of all breast cancers. They then examined the role of Akt in the onset and progression of breast cancer in the resulting offspring.

To their surprise, mice lacking two copies of the gene that produces Akt1 rarely had any tumors. Those mice that carried only one copy of the Akt1 gene developed some tumors, but they were small and developed more slowly. Mice with two copies of Akt1 rapidly developed significant cancer.

The finding was exciting because it told us that Akt1 is a potentially useful target for ErbB2-positive breast cancer, Dr. Pestell says. More interesting was that even if the mouse developed a tumor, it didnt develop metastases. We proved that there was a requirement for Akt1 in metastasis, which makes Akt1 an exciting target for metastatic breast cancer. We knew that Akt1 could play a role in cell growth and size, but the idea that it could p
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Contact: Steve Benowitz
steven.benowitz@jefferson.edu
215-955-5291
Thomas Jefferson University
9-Apr-2007


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