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Protein linked to therapy resistance in breast cancer
Date:9/11/2012

A gene that may possibly belong to an entire new family of oncogenes has been linked by researchers with the U.S. Department of Energy (DOE)'s Lawrence Berkeley National Laboratory (Berkeley Lab) to the resistance of breast cancer to a well-regarded and widely used cancer therapy.

One of the world's leading breast cancer researchers, Mina Bissell, Distinguished Scientist with Berkeley Lab's Life Sciences Division, led a study in which a protein known as FAM83A was linked to resistance to the cancer drugs known as EGFR-TKIs (Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors). Not only may this discovery explain the clinical correlation between a high expression of FAM83A and a poor prognosis for breast cancer patients, it may also provide a new target for future therapies.

"Resistance to EGFR-TKIs has limited their use for breast cancer treatment and until now the mechanisms behind this resistance have largely been a mystery," Bissell says. "We've demonstrated, both in cultured cells and in mice, that FAM83A has oncogenic properties and when overexpressed in cancer cells confers EGFR-TKI resistance and promotes the proliferation and invasion of tumors."

Bissell is the corresponding author along with Saori Furuta, also with Berkeley Lab's Life Sciences Division, of a paper describing this research in the Journal of Clinical Investigation (JCI). The paper is titled "FAM83A confers EGFR-TKI resistance in breast cancer cells and in mice." Other co-authors are Sun-Young Lee, Roland Meier, Marc Lenburg, Paraic Kenny and Ren Xu.

Therapeutic targeting of oncogenes can be an effective way to fight some cancers as evidenced in the successful use of EGFR-TKIs to fight lung cancer. However, EGFR-TKIs have not been effective for treating breast cancers. EGFR-TKIs work by blocking EGFR from adding a phosphate molecule to downstream signaling proteins, an action called phosphorylation that is a necessary step in the
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Contact: Lynn Yarris
lcyarris@lbl.gov
510-486-5375
DOE/Lawrence Berkeley National Laboratory
Source:Eurekalert  

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