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New Path from Estrogen to Survival in Breast Cancer Cells Described

After years of research, scientists at The University of Texas M. D. Anderson Cancer Center are now able to explain, in exquisite// molecular detail, how the estrogen hormone can help keep breast cancer cells alive.

In the Sept. 24 issue of the journal, Nature Cell Biology, they assign roles to a number of genes and proteins thought to play a part in breast cancer cell survival, and in the process, have identified potential molecular drug targets.

"It's a very complex story, but we have been able to bring together a number of basic discoveries from different fields of research to work out the basic mechanism by which estrogen can exert a pro-life effect on cancer cells," said the study's lead author, Edward T. H. Yeh, M.D., professor and chair of The University of Texas M. D. Anderson's Department of Cardiology.

Along the way, the researchers have provided some novel insights. One is that they have provided a role for breast cancer-associated protein 3 (BCA3), which had been recently found to be over-expressed in both breast and prostate cancers. Yeh and his team show that this protein, by itself, doesn't have any relationship to the cancer, but when modified by the protein NEDD8, can act like a tumor suppressor.

The researchers also found that SIRT1, a key protein involved in this molecular pathway, is a member of a family of proteins responsible for prolonging life span in both yeast and worms. "The fact that these molecules, which maintain life span in other species, has been found to be involved in suppressing cancer development seems important to us," Yeh said. "The reason people live longer is that they don't develop cancer as readily."

Players in this newly defined pathway are:

* BCA3, which had no known function. * NEDD8, a protein that can bind to other proteins and alter their function. * SENP8, a protease (enzyme) that can break bonds between other molecules. * SIRT1 * NFkB (Nucle
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