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

(SACRAMENTO, Calif.) In trying to find out why HER2-positive breast cancer can be more aggressive than other forms of the disease, UC Davis Cancer Center researchers have surprisingly discovered that HER2 itself is the culprit. By shutting down its own regulator gene, HER2 creates a permissive environment for tumor growth.

Building on recent research showing that the regulator labeled LRIG1 and commonly called "Lig-1" limits the growth-promoting signals of HER2, the research team set out to clarify the role of Lig-1 in breast cancer.

They found that, when compared to healthy breast tissue, the regulator is significantly suppressed.

"This suppression assists HER2 in its own over-expression and in driving the growth of cancer cells," said Colleen Sweeney, associate professor of biochemistry and molecular medicine and senior author of the study, which appears in this month's issue of Cancer Research. "HER2 is clearly taking an active role its own ability to be successful in promoting cancer."

Sweeney added that the study results could lead to new treatments aimed at restoring or replacing functions of the regulator. This is good news for patients because, in addition to being more aggressive, HER2-positive breast cancer tends to be less responsive to currently available treatments. The gene is over-expressed in about one-quarter to one-third of breast cancer cases.

Sweeney and colleagues began by studying mouse models of breast cancer with genomes that carry extra copies of HER2. They noticed an excess of HER2 protein in the resulting tumors, but it was not over-expressed in adjacent healthy tissues that also carried extra copies of the HER2 gene.

"That suggested to us that extra copies of HER2 alone are not enough to explain its over-expression. If it was, HER2 would have been over-expressed in both normal and tumor tissues from these mice," she said.

Given that observation, the team set out
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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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