Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Fox Chase Cancer Center researchers make significant discovery about function of p53

03.02.2003


Cancer researchers have known that the tumor-suppressor gene p53 is critical in preventing cells from dividing inappropriately and becoming tumors. But now, researchers at Fox Chase Cancer Center have established that the ability of the p53 gene to perform its job depends on the type of p53 within each cell. This and another new finding about p53, published in Nature Genetics (Feb. 3, 2003 online version, March 2003 print version), have implications for tailoring chemotherapy, designing new cancer treatments, and understanding how to treat cancer in certain populations.



“The existence of two variants, or polymorphisms, of p53 isn’t new, but we’ve discovered that the variant type in each cell can influence its tumor-suppressor ability,” explains senior author Maureen Murphy, Ph.D., a molecular biologist in the pharmacology department of Fox Chase Cancer Center, Philadelphia, Pa.

When functioning properly, p53 polices cells for problems such as errant cellular growth, the hallmark of human cancer. If such harmful factors are present, p53 triggers the process of programmed cell death (known as apoptosis)-in effect, causing the “bad” cells to self-destruct. Alterations, or mutations, in this gene have been found in more than 60 percent of human cancers.


Murphy and her colleagues have known about the two p53 variants, but how the differences affect p53’s ability to suppress tumor development was not previously understood until now.

“People have one form or another of p53,” says Murphy. “The p53 variant containing the amino acid called arginine is better at killing out-of-control cells. The other p53 variant with the amino acid proline is less capable of stopping errant cells. When we asked if the two forms might function differently, the answer was a resounding yes.

“In terms of treating cancer, patients could potentially be typed for the kind of p53 they have, some day allowing physicians to tailor their therapy. If a patient has the arginine p53, which kills cells better, relatively less drugs might be needed for that person’s body to kill tumor cells. If another patient has the proline form, which is less active, relatively more drugs may be needed to fight the tumor.”

Although p53 variants have not received much attention from the biomedical community until now, epidemiologists have known that the proline form has an enhanced frequency in African Americans. This variant, which is less likely to set off programmed cell death, is more frequent in populations who live closer to the equator and have darker skin color. As a result, “p53 variants seem to differ according to ethnicity, and that might have implications for cancer treatment in different populations,” says Murphy.

The published research also redefines the function of p53. The p53 protein normally resides in the nucleus, and the way scientists have hypothesized its control of cell death is that it “turns on” the proteins that tell a cell to die or “turns off” the proteins that tell a cell to live. When the researchers couldn’t find a difference between the two forms with regard to activity inside the nucleus, they turned their attention to a little-studied area of p53 activity outside the nucleus—in the mitochondria, the energy storehouse of the cell.

“We looked at this and found a dramatic difference between the two forms,” recalls Murphy. They found that the arginine form, which is more efficient at killing cells, travels out of the nucleus better and into the mitochondria, where p53 functions to kill the cell.

Murphy adds, “Not only did we find a common polymorphism that influences tumor suppression, we also found that this seemingly obscure activity is at the center of how this protein kills cells.”

By bringing the mitochondrial pathway of cell death to the forefront of research, the investigators suggest that drugs could be designed to put p53 directly into the mitochondria or enable the cell to put it there. In the paper, they begin to test this hypothesis. They showed that if a drug is administered that prevents p53 from going to the mitochondria, then it inhibits the ability of p53 to kill a cell. Future efforts will focus on identifying drugs that enhance the ability of p53 to go to the mitochondria.


Fox Chase Cancer Center, one of the nation’s first comprehensive cancer centers designated by the National Cancer Institute in 1974, conducts basic and clinical research; programs of prevention, detection and treatment of cancer; and community outreach. For more information about Fox Chase activities, visit the Center’s web site at www.fccc.edu or call 1-888-FOX CHASE.

"The codon 72polymorphic variants of p53 demonstrate significant differences in apoptotic potential" Nature Genetics (Feb. 3, 2003 online version, March 2003 print version). http://press.nature.com.

This research was conducted equally by Patrick Dumont, a postdoctoral fellow in the Murphy lab, and Julie Leu, a postdoc in the lab of Donna L. George, from the Department of Genetics at the University of Pennsylvania School of Medicine. Anthony C. Della Pietra III from the Murphy lab also participated in the research.


Karen Mallet | EurekAlert!
Further information:
http://www.fccc.edu/
http://press.nature.com

More articles from Health and Medicine:

nachricht Satellites, airport visibility readings shed light on troops' exposure to air pollution
09.12.2016 | Veterans Affairs Research Communications

nachricht Oxygen can wake up dormant bacteria for antibiotic attacks
08.12.2016 | Penn State

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

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...

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

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>