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Discovery Could Help Understand Breast-Cancer Therapies

CHAMPAIGN, Ill. -- Breast-cancer researchers at the University of Illinois have identified four amino acids viewed as leading actors in the binding of estrogen and anti-estrogen hormones to receptor proteins in the female reproductive system.

The findings could prove to be crucial in efforts to understand how the receptors respond to drug therapies and how they become resistant to tamoxifen, which, for 20 years, has been the anti-estrogen agent most commonly used against breast cancer in the United States, said lead researcher Benita Katzenellenbogen, a professor of molecular and integrative physiology.

The research was published in the Aug. 16 issue of The Journal of Biological Chemistry. The authors were Katzenellenbogen, who on Oct. 18 will receive the 1996 Komen Scientific Distinction Award from the Susan G. Komen Breast Cancer Foundation in Dallas; her husband, John Katzenellenbogen, professor of chemistry; Kirk Ekena, postdoctoral researcher; and Karen E. Weis, research associate.

The estrogen receptor is a protein containing about 600 amino acids. It takes in estrogen, providing the transcription signal (the message system) for biological activity important in bone maintenance, especially for postmenopausal women, and for cardiovascular protection. But estrogen also increases the risk of breast cancer in some women.

"We've identified portions of the hormone-binding domain of this protein that appear to be critical sites for binding with the hormone," Benita Katzenellenbogen said. "We've shown that if one alters one of these four amino acids then one eliminates the ability of estrogen to bind, and as a consequence one also eliminates the ability of these receptors to act as transcriptional regulators."

The research, funded by the National Institutes of Health, was conducted using a molecular biological technique called alanine-scanning mutagenesis, in which a different form of amino acid is substituted one at a
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Contact: Jim E. Barlow, Life Sciences Editor
b-james3@uiuc.edu
217-333-5802
University of Illinois at Urbana-Champaign
3-Oct-1996


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