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In breast cancer metastasis, researchers identify possible drug target
Date:1/27/2013

The spread of breast cancer to distant organs within the body, an event that often leads to death, appears in many cases to involve the loss of a key protein, according to UC San Francisco researchers, whose new discoveries point to possible targets for therapy.

In the January 27, 2013 online edition of Nature Cell Biology, UCSF scientists describe for the first time how the protein, known as GATA3 which is abnormal or absent in many cases of human breast cancer normally acts downstream in biochemical pathways to prevent the distant spread of cancer, an event called metastasis.

The discovery points to a biochemical control point that simultaneously holds in check several key events required for tumor cells to successfully spread.

"When GATA3 is present, it turns off many genes that are active in metastasis," said Zena Werb, PhD, a UCSF professor of anatomy who led the research. "We now have identified the molecular mechanisms involved."

The key finding of the new study is that GATA3 acts downstream biochemically to activate a molecule obscure until now called microRNA29b. MicroRNA29b in turn stops protein production from other genes that play vital roles in metastasis.

The absence or loss of GATA3 can free cancerous cells to break free from their defined roles and tethers within a tumor, to move away from the tumor mass, to induce cancer-promoting inflammation, and to stimulate the development of new blood vessels that can help spreading cancerous cells regrow as tumors in new locations.

"People knew that some of these genes were turned on in some cancers, but they did not know they were turned on because GATA3 and microRNA29b were turned off," Werb said. "If you have 20 genes that are becoming less active all at once due to microRNA29b, it could have a profound effect."

Working with mice, the researchers found that restoring microRNA29b to one of the most deadly types of breast c
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Contact: Jeffrey Norris
jeff.norris@ucsf.edu
415-502-6397
University of California - San Francisco
Source:Eurekalert  

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