Study Reveals Molecular Genetic Mechanisms Driving Breast Cancer Progression
News Apr 04, 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.
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.”
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.
Analytical Tool Predicts Disease-Causing GenesNews
Predicting genes that can cause disease due to the production of truncated or altered proteins that take on a new or different function, rather than those that lose their function, is now possible thanks to an international team of researchers that has developed a new analytical tool to effectively and efficiently predict such candidate genes.
Single Gene Change in Gut Bacteria Alters Host MetabolismNews
Scientists have found that deleting a single gene in a particular strain of gut bacteria causes changes in metabolism and reduced weight gain in mice. The research provides an important step towards understanding how the microbiome – the bacteria that live in our body – affects metabolism.READ MORE
High Fruit and Veg Consumption May Reduce Breast Cancer RiskNews
Women who eat a high amount of fruits and vegetables each day may have a lower risk of breast cancer, especially of aggressive tumors, than those who eat fewer fruits and vegetables, according to a new study led by researchers from Harvard T.H. Chan School of Public Health.READ MORE