Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


MIT biologists find that restoring the gene for cancer protein p53 slows spread of advanced tumors

In a new study to be published in the Nov. 25 issue of Nature, MIT cancer biologists show that restoring the protein p53's function in mice with lung cancer has no effect early in tumor development, but restoring the function later on could prevent more advanced tumors from spreading throughout the body.

Cancer researchers have known since the 1980s that p53 plays a critical role in protecting cells from becoming cancerous. P53 is defective in about half of all human cancers; when it functions correctly, it appears to suppress tumor formation by preventing cells with cancer-promoting mutations from reproducing.

Knowing p53's critical role in controlling cancer, researchers have been trying to develop drugs that restore the protein's function, in hopes of reestablishing the ability to suppress tumor growth. One such drug is now in clinical trials.

The findings of this new study suggest that drugs that restore p53 function could help prevent aggressive lung cancers from metastasizing, though they might spare benign tumor cells that could later turn aggressive. "Even if you clear the malignant cells, you're still left with benign cells harboring the p53 mutation," says David Feldser, lead author of the paper and a postdoctoral fellow at the David H. Koch Institute for Integrative Cancer Research at MIT.

However, such drugs are still worth pursuing because they could prolong the life of the patient, says Feldser, who works in the lab of Koch Institute Director Tyler Jacks, senior author of the paper. The research was funded by the Howard Hughes Medical Institute.

P53 is known to control the cell cycle, which regulates cell division. In particular, the protein stops a cell from dividing when its DNA is damaged. P53 then activates DNA repair systems, and if the damage proves irreparable, it instructs the cell to commit suicide.

Without p53, cells can continue dividing even after acquiring hazardous mutations. Eventually, after a cell accumulates enough mutations, it becomes cancerous. Cancer biologists believe that sustained inactivation of p53 and other tumor suppressors is necessary for cancers to become advanced.

In the new Nature study, the MIT researchers studied mice that are genetically engineered to develop lung tumors shortly after birth. Those mice also have an inactive form of the p53 gene, but the gene includes a genetic "switch" that allows the researchers to turn it back on after tumors develop.

At first, the researchers turned on p53 in mice that were four weeks old and had developed tumors known as adenomas, which are benign. To their surprise, restoring p53 had no effect on the tumors.

Next they turned on p53 in another group of tumor-prone mice, but they waited until the mice were 10 weeks old. At this point, their tumors had progressed to adenocarcinomas, a malignant type of cancer. In these mice, turning on p53 cleared the malignant cells, but left behind cells that had not become malignant.

This suggests that the p53 signaling pathway is recruited only when there is a lot of activity from other cancer genes. In benign tumors, there is not enough activity to engage the p53 system, so restoring it has no effect on those tumors. In the malignant tumor cells, reactivated p53 eliminates cells with too much activity in a signaling pathway involving mitogen-activated protein kinase (MAPK), which is often overactive in cancer cells, leading to uncontrolled growth.

The MIT researchers are now looking for drugs that reactivate mutant forms of p53, and also plan to study whether tumors that have metastasized would be vulnerable to p53 restoration.

Source: "Stage-specific sensitivity to p53 restoration during lung cancer progression," by David M. Feldser, Kamena K. Kostova, Monte M. Winslow, Sarah E. Taylor, Chris Cashman, Charles A. Whittaker, Francisco J. Sanchez-Rivera, Rebecca Resnick, Roderick Bronson, Michael T. Hemann, and Tyler Jacks. Nature, 25 November 2010.

Funding: The Howard Hughes Medical Institute

Jen Hirsch | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Gene therapy shows promise for treating Niemann-Pick disease type C1
27.10.2016 | NIH/National Human Genome Research Institute

nachricht 'Neighbor maps' reveal the genome's 3-D shape
27.10.2016 | International School of Advanced Studies (SISSA)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

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...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

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

How nanoscience will improve our health and lives in the coming years

27.10.2016 | Materials Sciences

OU-led team discovers rare, newborn tri-star system using ALMA

27.10.2016 | Physics and Astronomy

'Neighbor maps' reveal the genome's 3-D shape

27.10.2016 | Life Sciences

More VideoLinks >>>