Kimmel Cancer Center director Richard Pestell, M.D., Ph.D., professor and chair of cancer biology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, and colleagues genetically engineered mice to lack the protein Akt1, which normally plays a role in keeping cells alive by interfering with programmed cell death. Breast and other cancers make an overabundance of the protein, and it’s thought to potentially affect survival of breast and other cancer cells as well.
To test that hypothesis, Dr. Pestell and his team bred the mice missing the gene for Akt1 with other mice that overexpressed the HER2-neu (ErbB2) oncogene, which leads to approximately 25 percent of all breast cancers. They then examined the role of Akt in the onset and progression of breast cancer in the resulting offspring.
To their surprise, mice lacking two copies of the gene that produces Akt1 rarely had any tumors. Those mice that carried only one copy of the Akt1 gene developed some tumors, but they were small and developed more slowly. Mice with two copies of Akt1 rapidly developed significant cancer.
“The finding was exciting because it told us that Akt1 is a potentially useful target for ErbB2-positive breast cancer,” Dr. Pestell says. “More interesting was that even if the mouse developed a tumor, it didn’t develop metastases. We proved that there was a requirement for Akt1 in metastasis, which makes Akt1 an exciting target for metastatic breast cancer. We knew that Akt1 could play a role in cell growth and size, but the idea that it could play a role in migration and metastasis was an unexpected new finding,”
The researchers also proved how, showing that Akt1 causes the cancer cells to secrete a factor – CXCL16 – that promotes breast cancer cell migration. Without Akt, cancer cells failed to migrate. They also showed that deleting Akt1 completely blocked breast cancer metastasis to the lungs, while mice that expressed Akt1 died from lung metastasis.
While scientists have looked at Akt as a drug target, notes Arthur Pardee, Ph.D., professor emeritus of medical oncology at the Dana-Farber Cancer Institute in Boston, its role in metastasis is less emphasized. “Blocking this with anti-Akt drugs might provide a novel treatment, especially against early cancers,” he says.
While the monoclonal antibody drug Herceptin has been very successful in treating ErbB2-positive breast cancer, patients can relapse, Dr. Pestell notes, and other drug targets are needed. The newly found secreted factor may prove to be such a target.
“We’d like to find a way of blocking CXCL16 production and see if it’s true in human breast cancers,” Dr. Pestell says. “Right now we are looking at patients’ samples to see whether this is important in promoting metastatic breast cancer of other types.”
Steve Benowitz | EurekAlert!
Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
19.07.2018 | Earth Sciences
19.07.2018 | Power and Electrical Engineering
19.07.2018 | Materials Sciences