Study reveals molecular genetic mechanisms driving breast cancer progression

Share Your Favorites!

Original Source Here


DALLAS – April 3, 2015 – Researchers at UT Southwestern Medical Center have uncovered how the body’s inflammatory response can alter how estrogen promotes the growth of breast cancer cells. IMAGE

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 combination — the steroid hormone estradiol and the proinflammatory cytokine tumor necrosis factor alpha (TNFα) — act to expand the number of sites where estrogen receptor alpha (ERα) 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. “Since the altered pattern of gene expression can predict outcomes in breast cancer, there are important diagnostic and prognostic implications.”

The findings are published online and in the journal Molecular Cell.

Approximately 12.3 percent of women will be diagnosed with breast cancer at some point during their lifetime, and nearly 2.9 million women are living with breast cancer in the United States, according to statistics from the National Cancer Institute (NCI). About 232,670 new cases were reported in 2014, constituting about 14 percent of all new cancer cases. About 40,000 deaths were attributed to breast cancer in 2014.

Cancer cells release signals that can prompt the body to respond with an inflammatory response. As part of this response, TNFα is released and can impact the growth of the cancer cells. Previous studies suggested that inflammation might exacerbate the cancer, while the present study suggests that, in some cases, it might actually promote a better outcome. The study revealed that, when present together, TNFα and estradiol cause ERα, a nuclear transcription factor that is present in about two-thirds of breast cancers (so-called ER+ cancers), to bind to new sites in the genome where the protein does not bind with either TNFα or estradiol alone. These new ERα binding sites allow altered gene expression and, for some subtypes of breast cancers, inhibit the growth of cancer cells.

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, said Dr. Kraus, Professor and Vice Chair for Basic Sciences in Obstetrics and Gynecology, Professor of Pharmacology, and holder of the Cecil H. and Ida Green Distinguished Chair in Reproductive Biology Sciences.


The mission of the Cecil H. and Ida Green Center for Reproductive Biology Sciences, endowed by Cecil and Ida Green in 1974, is to promote and support cutting-edge, integrative, and collaborative basic research in female reproductive biology, with a focus on signaling, gene regulation, and genome function.

Other UT Southwestern researchers involved in the work were postdoctoral researcher Dr. Hector Franco and computational biologist Anusha Nagari.

The work was supported by a postdoctoral fellowship from the American Cancer Society – Lee National Denim Day Fellowship and a grant from the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health.

UT Southwestern’s Harold C. Simmons Comprehensive Cancer Center is the only National Cancer Institute-designated cancer center in North Texas and one of just 68 NCI-designated cancer centers in the nation. The Simmons Cancer Center includes 13 major cancer care programs with a focus on treating the whole individual with innovative treatments, while fostering groundbreaking research that has the potential to improve patient care and prevention of cancer worldwide. In addition, the Center’s education and training programs support and develop the next generation of cancer researchers and clinicians.

The Simmons Cancer Center is among only 30 U.S. cancer research centers to be named a National Clinical Trials Network Lead Academic Participating Site, a prestigious new designation by the NCI, and the only Cancer Center in North Texas to be so designated. The designation and associated funding is designed to bolster the cancer center’s clinical cancer research for adults and to provide patients access to cancer research trials sponsored by the NCI, where promising new drugs often are tested.

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty includes many distinguished members, including six who have been awarded Nobel Prizes since 1985. Numbering approximately 2,800, the faculty is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in 40 specialties to about 92,000 hospitalized patients and oversee approximately 2.1 million outpatient visits a year.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Jonathon Fulkerson
Follow me
This entry was posted in Articles, Cancer, Papers on by .

About Jonathon Fulkerson

After 15+ years as an IT professional. Jonathon decided to return to school in hopes of one day troubleshooting the most universal problem effecting all. Death, pain, and suffering by aging. As an undergraduate he is currently performing research in Dr. Richard Bennetts lab at the University of Southern Indiana, as well as volunteering for various organizations including the Buck Institute for research on Aging.

1 thought on “Study reveals molecular genetic mechanisms driving breast cancer progression

Leave a Reply

Your email address will not be published.