“This cell-based study is exciting because it suggests these compounds are likely to be effective in tumors that remain dependent on estrogen for growth but are resistant to current therapies,” said principal investigator David J. Shapiro, a professor of biochemistry in the School of Molecular and Cellular Biology at the University of Illinois.
Although multiple factors contribute to the development of breast cancer, estrogens play a key role in the growth of many tumors. More than 80 percent of breast cancer tumors in women over age 45 are activated by estrogen by way of a protein called an estrogen receptor. When estrogen binds to the receptor, this “estrogen-receptor complex” latches on to DNA and prompts it to transcribe the RNA blueprints for new proteins that promote cell growth, migration and division.
Current therapies for estrogen-receptor-positive (ER-positive) breast cancers include the use of drugs, such as tamoxifen, that interfere with estrogen’s ability to bind to the estrogen receptor. Over time, however, ER-positive breast cancer tumors become resistant to tamoxifen. In some resistant tumors, tamoxifen even begins to act like estrogen and actually stimulates tumor growth.
“Tamoxifen is useful in that it is very effective at blocking recurrence of breast cancer in patients for whom the entire tumor is removed,” Shapiro said. “But for patients who still have existing tumors, eventually those tumors will become resistant.”
Shapiro’s team sought to target other steps in the pathway of estrogen action. Using a technique they developed that can quickly determine whether the target DNA is – or is not – bound by the estrogen-receptor complex, the team was able to screen a long list of potential therapeutic compounds to see if they inhibited the binding of the complex to the DNA. They then tested these agents in ER-positive breast cancer cells.
The team identified several compounds that reduce the binding of estrogen-receptor complex to the regulatory regions of genes that are normally activated by this complex. These agents effectively retarded production of the proteins that promote the growth and proliferation of ER-positive breast cancer cells.
“These small molecules specifically block growth of estrogen-dependent breast cancer cells with little or no effect on other cells,” Shapiro said. “This work sets the stage for further development and testing of these inhibitors.”
The collaboration included researchers from the University of Colorado, the University of North Carolina, and the departments of molecular and integrative physiology and of chemistry at Illinois.
This basic research study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health.
Diana Yates | University of Illinois
Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory
Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP
Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.
Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
09.12.2016 | Life Sciences
09.12.2016 | Ecology, The Environment and Conservation
09.12.2016 | Health and Medicine