Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


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

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:

Further reports about: MDM2 Mutant Mutation degrade p53

More articles from Life Sciences:

nachricht When fat cells change their colour
28.10.2016 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht Aquaculture: Clear Water Thanks to Cork
28.10.2016 | Technologie Lizenz-Büro (TLB) der Baden-Württembergischen Hochschulen 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 light sources made of 2D materials

Physicists from the University of Würzburg have designed a light source that emits photon pairs. Two-photon sources are particularly well suited for tap-proof data encryption. The experiment's key ingredients: a semiconductor crystal and some sticky tape.

So-called monolayers are at the heart of the research activities. These "super materials" (as the prestigious science magazine "Nature" puts it) have been...

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

All Focus news of the innovation-report >>>



Event News

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

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Prototype device for measuring graphene-based electromagnetic radiation created

28.10.2016 | Power and Electrical Engineering

Gamma ray camera offers new view on ultra-high energy electrons in plasma

28.10.2016 | Physics and Astronomy

When fat cells change their colour

28.10.2016 | Life Sciences

More VideoLinks >>>