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UC Davis researchers discover a key to aggressive breast cancer
Date:10/30/2008

to determine what, exactly, created the permissive environment for HER2 over-expression. Given its tumor-suppressor role, Lig-1 levels were compared in the mouse models.

They found that Lig-1 was greatly diminished in tumor tissues when compared to the normal tissues. The researchers next conducted a series of laboratory experiments using human breast cancer cell lines and a technique called RNA interference that allows for selective depletion of cellular proteins.

Interestingly, they found the same results in the human breast cancers that they found in mice. In fact, 60 percent of 67 tumors analyzed showed a loss of the Lig-1 protein and its levels were, on average, 33 percent lower in tumor tissue versus healthy breast tissue.

"There was a clear inverse relationship between Lig-1 and HER2," said Sweeney. "When we depleted Lig-1, cancer cells grew almost 50 percent faster, while the opposite occurred when we restored Lig-1 to healthy levels. We also found that depleting HER2 levels resulted in an increase in Lig-1 levels, while activating HER2 resulted in Lig-1 depletion."

According to Sweeney, the results may help explain why, even among patients with HER2-positive breast cancer, the disease process can vary dramatically.

"We think Lig-1 levels could be linked to prognosis. Patients with more of the regulator gene's functions intact are going to have a better outcome than those with less," she said.

Results of the current study further support the notion that Lig-1 serves as a tumor suppressor gene, though more work is needed to confirm this outcome. Sweeney and her team are gathering more evidence to support this theory and to determine whether or not Lig-1 levels are truly predictive of outcome for HER2-positive patients. If so, it will suggest that, while this type of test is not available today, these patients should in the future be screened for Lig-1 activity in order to better define treatment subgroup
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Contact: Karen Finney
karen.finney@ucdmc.ucdavis.edu
916-734-9064
University of California - Davis - Health System
Source:Eurekalert

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