Surprisingly, one of the partner proteins is known as c-MYC, a gene activator that has long been associated with cancer development but was not known to interact with estrogen during tumor progression.

The study, by researchers at The Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, answers the puzzling question of how estrogen can turn on some genes and turn off others during cancer progression.

"Our results indicate that the interaction of estrogen with one of seven different partner proteins determines whether the gene is activated or suppressed," says coauthor Ramana V. Davuluri, assistant professor of bioinformatics and computational biology.

The findings could also reveal potential new drug targets and lead to a test to identify breast-cancer patients with tumors that are likely to become resistant to hormonal therapies such as tamoxifen and aromatase inhibitors.

The research is published in the Feb. 3 issue of the journal Molecular Cell.

The study is unusual because it used microarray technology and mathematical modeling to predict which cell proteins work with estrogen to contribute to breast cancer development, and then used more traditional experimental biology to verify one of the predictions.

"We conducted this study with almost equal contributions from computational scientists and experimental scientists," says principal investigator and corresponding author Tim Hui-Ming Huang, professor of human cancer genetics.

"This strategy, in which computational predictions are verified by the bench scientist, will be a trend for future cancer research," Huang says.

Scientists have known for decades that estrogen plays a key role in the developme
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Contact: Eileen Scahill
Eileen.Scahill@osumc.edu
614-293-3737
Ohio State University
2-Feb-2006