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Previously unseen switch regulates breast cancer response to estrogen
Date:5/8/2008

A tiny modification called methylation on estrogen receptors prolongs the life of these growth-driving molecules in breast cancer cells, according to research by scientists at Emory University's Winship Cancer Institute.

The results are published in the May 9, 2008 issue of the journal Molecular Cell.

Most breast cancers contain estrogen receptors, which enable them to grow in the presence of the hormone estrogen. Their presence can determine whether tumors will respond to the estrogen-blocking drug tamoxifen.

The finding will help researchers sort out how mutations change the estrogen receptor's function and allow some breast cancers to resist tamoxifen, says Paula Vertino, PhD, associate professor of radiation oncology at Emory University School of Medicine.

"The problem is that a significant fraction of estrogen receptor positive tumors don't respond to tamoxifen," Vertino says. "Development of new drugs that interfere with the methylation of the estrogen receptor may be an alternative way to treat those tumors."

Until recently, scientists thought methylation enzymes acted only on DNA molecules or on histones, proteins that bundle DNA into spool-like packages. Methylation enzymes add tags called methyl groups to other molecules, influencing their ability to turn genes on or off.

Vertino and her colleagues found that one of the modification enzymes, called SET7, methylates a flexible part of the estrogen receptor. When they created breast cancer cells with reduced levels of SET7, the estrogen receptor molecules lasted only half as long and were less effective in turning on genes.

Vertino's team showed that a mutation in the estrogen receptor found in more aggressive breast tumors interferes with methylation in cells. Also, the methylation appears in exactly the same spot where another protein called BRCA1 adds a different kind of regulatory marking, and may block BRCA1's restrictive effects on t
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Contact: Vince Dollard
vdollar@emory.edu
404-778-4580
Emory University
Source:Eurekalert

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