“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
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
17.01.2017 | Earth Sciences
17.01.2017 | Materials Sciences
17.01.2017 | Architecture and Construction