Combination of Estradiol & TNFα May Be Salutary in Some ER+ Breast Cancers

Researchers at the University of Texas (UT) Southwestern Medical Center have uncovered how the body's inflammatory response can alter how estrogen promotes the growth of breast cancer cells. UT Southwestern researchers identified how a combination of signaling molecules inhibits the growth of breast cancer cells, improving clinical outcomes for some subtypes of breast cancers. The molecule combination – of the steroid hormone estradiol and the proinflammatory cytokine tumor necrosis factor alpha (TNFα) -- acts to expand the number of sites where estrogen receptor alpha (ERα) (image) can bind to the genome in breast cancer cells. The new sites of ERα binding turn new genes on and off, which alters the growth response of the breast cancer cells, inhibiting their growth and improving clinical outcomes in certain cases. The newly identified gene set can be used as a biomarker that can help physicians determine who is at risk and how they might react to certain therapies. "Our study uncovered the molecular mechanisms that alter the expression of the new set of genes in response to estradiol and TNFα, and identified potential target genes for future therapy," said senior author Dr. W. Lee Kraus, Director of the Cecil H. and Ida Green Center for Reproductive Biology Sciences, Professor of Obstetrics and Gynecology, and a member of the Harold C. Simmons Comprehensive Cancer Center, all at UT Southwestern. "Because the altered pattern of gene expression can predict outcomes in breast cancer, there are important diagnostic and prognostic implications." The findings were published in an open-access article in the April 2, 2015 issue of Molecular Cell. The article is titled “TNFα Signaling Exposes Latent Estrogen Receptor Binding Sites to Alter the Breast Cancer Cell Transcriptome.”
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