The researchers, led by Kimmel Cancer Center director Richard Pestell, M.D., Ph.D., hope the newly found connection will aid in better understanding the development of prostate cancer and lead to new drugs against the disease.
SIRT1 is a member of a family of enzymes called sirtuins that have far-reaching influence in all organisms, including roles in metabolism, gene expression and aging.
“We know that sirtuins play a role in aging, and that the risk for prostate cancer increases with aging, but no one has ever linked the two until now,” says Dr. Pestell, who is also professor and chair of cancer biology at Jefferson Medical College.
“We’ve shown that by making a prostate cancer with cells overexpressing a mutation for the androgen receptor, which is resistant to current forms of therapy, we can almost completely block the growth of these cells with SIRT1,” he says. Dr. Pestell and his team report their findings in November in the journal Molecular and Cellular Biology.
According to Dr. Pestell, prostate cancer cells can express a mutation that makes patients resistant to current forms of treatment such as hormonal therapy. Such therapy focuses on inactivating the androgen receptor by giving agents that shut off testosterone production.
In one experiment, the scientists took a series of mutations in androgen receptors from prostate cancer patients who are resistant to hormonal therapy and showed that SIRT1 blocks receptor activity, halting cancer growth. “We systematically tested each androgen receptor mutation,” Dr. Pestell explains. “These mutant receptors are resistant to current therapies and are all blocked by expression of SIRT1,” adding that prostate specific antigen (PSA) levels were used to confirm this. Rising PSA levels are frequently an indication of prostate cancer growth or recurrence, whereas falling levels indicate tumor shrinkage.
“This study shows that there is potentially new opportunity for these cancer patients with drugs that regulate SIRT1,” Dr. Pestell says.
“The discovery is a true breakthrough in our field,” says Chawnshang Chang, Ph.D., George Hoyt Whipple Professor of Pathology and Laboratory Medicine and professor of urology and of biochemistry at the University of Rochester.
Dr. Pestell and his co-workers also found a single amino acid within the androgen receptor that reacts with SIRT1’s enzymatic activity and proved in the laboratory that it was key to its cancer-halting effect. The work could lead to a model for drug screening, Dr. Pestell notes.
Steve Benowitz | EurekAlert!
Zap! Graphene is bad news for bacteria
23.05.2017 | Rice University
Discovery of an alga's 'dictionary of genes' could lead to advances in biofuels, medicine
23.05.2017 | University of California - Los Angeles
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.
In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...
Dental plaque and the viscous brown slime in drainpipes are two familiar examples of bacterial biofilms. Removing such bacterial depositions from surfaces is...
23.05.2017 | Event News
22.05.2017 | Event News
17.05.2017 | Event News
23.05.2017 | Physics and Astronomy
23.05.2017 | Life Sciences
23.05.2017 | Medical Engineering