Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Loosen leash on cancer protein ’watchdog,’ researchers say

06.01.2006


Scientists may have found a way to keep a protein "watchdog" on high alert to stop hereditary cancers from overrunning our bodies – if they can keep it on a leash of just the right length.



In a collaborative effort, a team of scientists including Purdue University’s Susan M. Mendrysa has found that one of the proteins found naturally in cells has the ability to halt the progression of intestinal tumors that arise from genetic predisposition. When the activity of this protein, known only by the technical name of p53, was artificially increased in the cells of laboratory mice, those known to have a hereditary predisposition for developing cancer showed a marked decrease in tumor development when compared with mice that had normal p53 activity.

The study also indicated that the treated mice did not suffer from the side effect the research team most feared: premature aging, which has been linked to overproduction of p53 in other studies. The discovery could assist in future human cancer treatments.


"It’s a question of balance," said Mendrysa (pronounced men-DRISS-ah), who is an assistant professor of basic medical sciences in Purdue’s College of Veterinary Medicine and co-lead author of the work. "The p53 protein has been long known as an effective weapon against cancers, but we know from previous research that we can’t just let it run rampant through the body without some very unpleasant side effects. But if we can give it just enough slack in its leash, it could help some patients from cancer-prone families from ever developing the disease."

The team’s research appears in the Jan. 1 issue of the scientific journal Genes and Development. Members of the group include the University of Wisconsin — Madison’s Kathleen A. O’Leary (co-lead author), Matthew K. McElwee and Jennifer Michalowski; the Fred Hutchinson Cancer Research Center’s Robert N. Eisenman; and the National Cancer Institute’s Mary Ellen Perry and Douglas A. Powell. When the group came together, Mendrysa said, they were primarily concerned with how they might stop their prospective protein watchdog from doing more harm than good.

"Research is turning up lots of possible inroads for combating disease these days, and other research teams had found that p53 was a good prospect for fighting cancer," she said. "With too little p53 protein, people and mice are more likely to develop cancer. But it’s not a panacea. Embryonic mice with too much p53 in their systems don’t survive gestation. Moreover, recent reports have suggested that high levels of p53 may accelerate aging. Having the wrong amount of p53 protein, therefore, leaves you with two potentially unappealing choices: Do you want to die early of cancer or die early from wearing your body out?"

The scientists theorized that the solution could lie with another protein the body produces naturally to keep p53 in check. This other protein, called Mdm2, keeps p53 inactive until it is needed, acting like a leash on a watchdog.

"p53 seems to be an important stress response gene that fights cancer when it works," Mendrysa said. "So we decided to see what we could do to increase p53’s activity without completely cutting its Mdm2 leash."

The scientists spent three years creating a strain of genetically modified mouse that only produced about 20 percent of the normal amount of Mdm2 protein, which is far less than they would have produced under ordinary conditions. The mice were created to answer a twofold question: Could increasing their levels of p53 delay or prevent tumor formation in living creatures, and would there be any negative consequences to the increase?

"We were primarily interested in the second part of the question when we began," Mendrysa said. "These mice had a family trait that typically made them develop cancerous lesions in their intestines, but our main goal was to see whether p53 sped up the aging process. Fortunately, we got more kinds of good news than we initially expected."

Mice with such a predisposition generally developed about 50 intestinal lesions within six months of birth, but mice modified for the study had only developed three or fewer within that time frame. Moreover, there was no sign that the mice had aged any faster than normal.

"We checked for the sort of characteristics that the elderly of many mammal species typically show – thinner skin, lower bone density, spinal hunching and the like," Mendrysa said. "We couldn’t find any differences between them and normal mice. And their cancer rates were dramatically lower than expected, which turned out to be the more significant finding of the study."

Mendrysa said the results were an enlightening fundamental discovery about suppressing hereditary intestinal cancers. But she also said the work raised a number of questions that would need to be answered before the research could translate into human therapy.

"These mice were genetically modified at conception to produce higher p53 levels, which is quite a different treatment than just giving normal mice a pill," Mendrysa said. "Also, mice in our study are not subject to the same stresses as, for example, a person working on Wall Street. It remains to be seen whether higher p53, in conjunction with other factors such as stress, could still lead to negative consequences such as aging. We’ll have to do a lot more work before this becomes a routine part of medicine’s anticancer toolkit.

"Essentially, this study validates Mdm2 as a potentially powerful chemopreventative for some kinds of hereditary cancer, and, if used properly, it might perform well without elevating the risks of aging that other groups have found. The benefits seem to outweigh the risks.

"We’d like to expand the research and look into how Mdm2 and p53 affect other cancer predispositions. If we can find the right length for the leash, someday we may be able to find a way to specify it without resorting to genetic modification. Then we might have a way to keep the watchdog on high alert."

This research was supported in part by the National Institutes of Health.

Mendrysa is affiliated with the Purdue Cancer Center. One of just seven National Cancer Institute-designated basic-research facilities in the United States, the center attempts to help cancer patients by identifying new molecular targets and designing future agents and drugs for effectively detecting and treating cancer. The center is part of the university’s Oncological Sciences Center in Discovery Park.

Writer: Chad Boutin, (765) 494-2081, cboutin@purdue.edu

Source: Susan M. Mendrysa, (765) 494-8622, mendrysa@purdue.edu

Purdue News Service: (765) 494-2096; purduenews@purdue.edu

Chad Boutin | EurekAlert!
Further information:
http://www.purdue.edu

More articles from Life Sciences:

nachricht Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht 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

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

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...

Im Focus: Quantum Particles Form Droplets

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...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

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,...

Im Focus: Molecules change shape when wet

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...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>