This week, researchers from the University of Texas Southwestern Medical Center in Dallas have released results from a clinical study in which they determined how the body’s inflammatory response can alter the way estrogen promotes the growth of certain breast cancer (BC) cells; a discovery that could result in improved clinical outcomes for specific subtypes of BC. The study, entitled, “TNFα Signaling Exposes Latent Estrogen Receptor Binding Sites to Alter the Breast Cancer Cell Transcriptome,” was published in the latest edition of the journal Molecular Cell.
The study was conducted in the lab of Dr. W. Lee Kraus, PhD, Director of the Cecil H. and Ida Green Center for Reproductive Biology Sciences, Professor and Vice Chair for Basic Sciences in the Department of Obstetrics and Gynecology, Professor in the Department of Pharmacology. The aim of Dr, Kraus’ work is to use an interdisciplinary approach to uncover and understand the connections between hormone-regulated gene expression and BC.
In this study Dr. Kraus and his colleagues looked at a combination of hormones that included:
- Estradiol: a steroid hormone.
- Tumor necrosis factor alpha (TNFα): a pro-inflammatory cytokine (cell signaling protein) of the immune system.
They analyzed the molecular crosstalk (effect of one component of a cell signaling pathway on another) between the estrogen and TNFα. They found that the signaling acts to expand the number of sites where estrogen receptor alpha (ERα) that is present in upwards of two-thirds of BCs (so-called ER+ cancers), can bind to the genome in BC cells. These new sites of ERα binding turn new genes on and off, this then alters the growth response of BC cells, inhibiting their growth and improving clinical outcomes in certain cases.
In a press release about the study, Dr. Kraus, stated “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. Since the altered pattern of gene expression can predict outcomes in BC, there are important diagnostic and prognostic implications.”
Dr. Kraus, continued “Since the effect only happens when the two are combined, researchers can use the altered gene expression patterns as an indicator that both agents are at work in the cancer and as a biomarker that may help determine who might be more at risk and how they might react to therapy,”