Featured Research

from universities, journals, and other organizations

Restoring gene for cancer protein p53 slows spread of advanced tumors, biologists find

Date:
November 25, 2010
Source:
Massachusetts Institute of Technology
Summary:
In a new study, 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.

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.

Funding was provided by the Howard Hughes Medical Institute.


Story Source:

The above story is based on materials provided by Massachusetts Institute of Technology. The original article was written by Anne Trafton, MIT News Office. Note: Materials may be edited for content and length.


Journal Reference:

  1. 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. Stage-specific sensitivity to p53 restoration during lung cancer progression. Nature, 2010; 468, 572-575 DOI: 10.1038/nature09535

Cite This Page:

Massachusetts Institute of Technology. "Restoring gene for cancer protein p53 slows spread of advanced tumors, biologists find." ScienceDaily. ScienceDaily, 25 November 2010. <www.sciencedaily.com/releases/2010/11/101124143415.htm>.
Massachusetts Institute of Technology. (2010, November 25). Restoring gene for cancer protein p53 slows spread of advanced tumors, biologists find. ScienceDaily. Retrieved July 24, 2014 from www.sciencedaily.com/releases/2010/11/101124143415.htm
Massachusetts Institute of Technology. "Restoring gene for cancer protein p53 slows spread of advanced tumors, biologists find." ScienceDaily. www.sciencedaily.com/releases/2010/11/101124143415.htm (accessed July 24, 2014).

Share This




More Health & Medicine News

Thursday, July 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Newsy (July 24, 2014) Sheik Umar Khan has treated many of the people infected in the Ebola outbreak, and now he's become one of them. Video provided by Newsy
Powered by NewsLook.com
Condemned Man's US Execution Takes Nearly Two Hours

Condemned Man's US Execution Takes Nearly Two Hours

AFP (July 24, 2014) America's death penalty debate raged Thursday after it took nearly two hours for Arizona to execute a prisoner who lost a Supreme Court battle challenging the experimental lethal drug cocktail. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com
China's Ageing Millions Look Forward to Bleak Future

China's Ageing Millions Look Forward to Bleak Future

AFP (July 24, 2014) China's elderly population is expanding so quickly that children struggle to look after them, pushing them to do something unexpected in Chinese society- move their parents into a nursing home. Duration: 02:07 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins