Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Stabilizing cancer-fighting p53 can also shield a metastasis-promoter

26.05.2008
M. D. Anderson research shows protecting p53 from degradation also defends its mutant

Efforts to protect the tumor-suppressor p53 could just as easily shelter a mutant version of the protein, causing cancer cells to thrive and spread rather than die, according to research by scientists at The University of Texas M. D. Anderson Cancer Center reported in the current issue of the journal Genes and Development.

"As we develop therapies to restore the function of p53, we need to make sure we first know what version of this gene is present in a patient's tumor and then decide how to treat it," said senior author Guillermina Lozano, Ph.D., professor and chair of M. D. Anderson's Department of Cancer Genetics.

The research shows that attempting to restore normal expression of p53 protein by blocking another protein that normally degrades p53 can have the perverse effect of protecting mutated p53 and promoting metastasis.

... more about:
»MDM2 »Mutant »Mutation »degrade »p53

The p53 gene is inactivated in many types of cancer. Its normal role is to halt the division of a defective cell and then force the cell to kill itself or deprive the cell of its ability to reproduce. As such, reactivation of p53 is thought to have great therapeutic potential.

Normally, p53 levels are low, but it springs into action in response to DNA damage or activation of cancer-promoting genes, or oncogenes.

Lozano, an expert on mouse models of human cancer, and colleagues developed mice with a specific mutation of p53 that mimics a common genetic mutation in human cancers. The mutated gene, called p53H, expresses a defective version of the p53 protein.

When mice had the p53H mutation on both genes (p53 H/H), the researchers found that the p53 protein was not detectable in normal tissue but was present in 79 percent of tumors. However, tumors in these mice did not metastasize.

Enter Mdm2, a protein whose normal job is to degrade p53 when it's no longer needed. Mdm2 also degrades the mutated version of the p53 protein.

The researchers developed p53 mutant mice that lacked one or both copies of Mdm2. Mice with the double-mutant p53 that also had no Mdm2 died sooner and developed more aggressive metastatic tumors than mice with only the p53 mutation.

The frequency of metastasis went from zero in the p53 H/H with normal Mdm2, to 9 percent in mice lacking one copy of Mdm2 to 17 percent in mice with no Mdm2. Metastasis - the invasive spread of cancer to other organs - causes 90 percent of all human cancer deaths.

Absence of a second tumor-suppressing gene, p16, also promotes stability of mutant p53.

"The importance of this study cannot be overemphasized," the researchers concluded. Drugs that try to protect normal p53 by inhibiting the p53-degrading protein Mdm2 also would protect mutant p53 "with dire consequences."

By the same token, chemotherapy that seeks to stabilize p53 could also stabilize the mutant version. Detecting the type of p53 present in a tumor is possible with current lab technology, Lozano said.

The study raises the possibility of suppressing cancer metastasis by eliminating mutant p53 stability, which the researchers note is more feasible than converting mutant p53 to the normal type.

Scott Merville | EurekAlert!
Further information:
http://www.mdanderson.org

Further reports about: MDM2 Mutant Mutation degrade p53

More articles from Life Sciences:

nachricht World’s Largest Study on Allergic Rhinitis Reveals new Risk Genes
17.07.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Plant mothers talk to their embryos via the hormone auxin
17.07.2018 | Institute of Science and Technology Austria

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First evidence on the source of extragalactic particles

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...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

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...

Im Focus: Breaking the bond: To take part or not?

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...

Im Focus: New 2D Spectroscopy Methods

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....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Microscopic trampoline may help create networks of quantum computers

17.07.2018 | Information Technology

In borophene, boundaries are no barrier

17.07.2018 | Materials Sciences

The role of Sodium for the Enhancement of Solar Cells

17.07.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>