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!
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
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...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy