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Researchers zero in on estrogen's role in breast-cancer cell growth

CHAMPAIGN, Ill. -- Why do estrogen-dependent breast-cancer cells grow and spread rapidly? Researchers at the University of Illinois at Urbana-Champaign say it may be because estrogen virtually eliminates levels of a vitally important regulatory protein.

In a paper that will appear in the Sept. 13 issue of the Proceedings of the National Academy of Sciences, the scientists report that human breast-cancer cells exposed to estrogen in their laboratory showed a dramatic reduction in numbers of a crucial nuclear receptor corepressor, a protein known as N-CoR (pronounced "en CORE"). They also found that the anti-estrogen drug tamoxifen, often used in breast-cancer treatments, encouraged N-CoR recovery, a beneficial activity. The paper was published online last week.

"Because estrogen has the ability to reduce the levels of N-CoR, estrogen then can promote the proliferation and progression of breast cancer, because the balance of co-activators and co-repressors involved in normal gene transcription is altered," said Benita S. Katzenellenbogen, a Swanlund Professor of Cell and Developmental Biology at Illinois. She also is a professor of molecular and integrative physiology.

The findings may have sweeping implications, said Katzenellenbogen and lead author Jonna Frasor, a postdoctoral researcher who joins the faculty of the department of physiology and biophysics in the U. of I. College of Medicine at Chicago this month.

For one, the mechanisms at play could explain at least some of the mixed results seen in women using estrogen and progesterone in hormone therapy, said Katzenellenbogen, who also is a professor in the U. of I. College of Medicine at Urbana-Champaign.

While numbers of N-CoR proteins fell to 20 percent of normal, the level of N-CoR's messenger RNA went untouched. The reduction of N-CoR followed an up regulation of the ubiquitin ligase Siah2, an enzyme that targets certain proteins for degradation, Frasor said.

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Contact: Jim Barlow, Life Sciences Editor
jebarlow@uiuc.edu
217-333-5802
University of Illinois at Urbana-Champaign
8-Sep-2005


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