Featured Research

from universities, journals, and other organizations

New understanding of how to prevent destruction of a tumor suppressor

Date:
December 14, 2009
Source:
Indiana University School of Medicine
Summary:
Researchers have determined how the protein Mdm2, which is elevated in late-stage cancers, disables genes that suppress the growth of tumors. The finding may lead to development of new drugs for late stage breast cancer and other difficult to treat malignancies.

This graphic depicts the hardwiring that causes Mdm2 to increase and bind and inactivate several proteins in cancer.
Credit: Lindsey Mayo, Ph.D., Indiana University School of Medicine

Researchers from the Indiana University School of Medicine and colleagues at the University of Texas Southwestern and Case Western University have determined how the protein Mdm2, which is elevated in late-stage cancers, disables genes that suppress the growth of tumors. The finding may lead to the development of new drugs for late stage breast cancer and other difficult to treat malignancies.

The investigators have identified a critical pathway that stimulates the production of Mdm2 causing an increase in the level of protein that bind to p53, the most common tumor suppressor, as well as other tumor suppressors, and extinguishes tumor suppression activity. The study appears in the January 2010 issue of the Journal of Clinical Investigation.

Principal investigator Lindsey Mayo, Ph.D., assistant professor of pediatrics at the Herman B Wells Center for Pediatric Research at the IU School of Medicine and an Indiana University Melvin and Bren Simon Cancer Center member, says that keeping Mdm2 inactive and preventing the destruction of the tumor suppressor that Mdm2 targets, is critical to preventing cancer from spreading within the body.

To explain the role of Mdm2 and how the newly identified pathways function, Dr. Mayo uses the analogy of a florescent ceiling fixture in which Mdm2 is the fluorescent bulb. "Initially, it was only known that the light was on, not how it was turned on. We discovered the wall switch and wires that connect to the light fixture to turn on the fluorescent light."

"This work provides new evidence about an important mechanism that tumor cells use to promote metastasis. While it has long been known that the loss of tumor suppressor activity triggers cancer, knowledge of how these cancer inhibitors are turned on and off has eluded researchers. Understanding the signaling pathways that elevate Mdm2 is critical to preventing cancer from spreading within the body and key to attacking many late stage cancers," said Dr. Mayo, a molecular biochemist who studies the mechanisms that control tumor suppressors.

While it is too early to speculate on which chemical compounds may yield successful drugs, Dr. Mayo says this new insight into Mdm2 and its pathways provides a useful roadmap to stimulate development of new compounds which could bind to Mdm2 to inhibit the protein and stop its attacks on tumor suppressors.

In addition to Dr. Mayo, co-authors of the study, which was funded by the National Cancer Institute, are medical student Jacob A. Eitel, graduate student Christopher N. Batuello, Khadijeh Bijangi-Vishehsaraei, Ph.D. and Karen E. Pollok, Ph.D. of the IU School of Medicine, Shinako Araki, Ph.D. , Xian-Jin Xie Ph.D., and David A. Boothman, Ph.D. of the University of Texas Southwestern Medical Center; and David Danielpour, Ph.D. of Case Western Reserve University.

The Wells Center is the research arm of the IU School of Medicine Department of Pediatrics and Riley Hospital for Children. The IU School of Medicine, the Wells Center, Riley Hospital and the IU Simon Cancer Center are located on the campus of Indiana University-Purdue University Indianapolis.


Story Source:

The above story is based on materials provided by Indiana University School of Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. Shinako Araki, Jacob A. Eitel, Christopher N. Batuello, Khadijeh Bijangi-Vishehsaraei, Xian-Jin Xie, David Danielpour, Karen E. Pollok, David A. Boothman and Lindsey D. Mayo. TGF-β1–induced expression of human Mdm2 correlates with late-stage metastatic breast cancer. Journal of Clinical Investigation, 2010; 120 (1): 1-14 DOI: 10.1172/JCI39194

Cite This Page:

Indiana University School of Medicine. "New understanding of how to prevent destruction of a tumor suppressor." ScienceDaily. ScienceDaily, 14 December 2009. <www.sciencedaily.com/releases/2009/12/091201182612.htm>.
Indiana University School of Medicine. (2009, December 14). New understanding of how to prevent destruction of a tumor suppressor. ScienceDaily. Retrieved July 29, 2014 from www.sciencedaily.com/releases/2009/12/091201182612.htm
Indiana University School of Medicine. "New understanding of how to prevent destruction of a tumor suppressor." ScienceDaily. www.sciencedaily.com/releases/2009/12/091201182612.htm (accessed July 29, 2014).

Share This




More Health & Medicine News

Tuesday, July 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Generics Eat Into Pfizer's Sales

Generics Eat Into Pfizer's Sales

Reuters - Business Video Online (July 29, 2014) Pfizer, the world's largest drug maker, cut full-year revenue forecasts because generics could cut into sales of its anti-arthritis drug, Celebrex. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Nigeria Ups Ebola Stakes on 1st Death

Nigeria Ups Ebola Stakes on 1st Death

Reuters - Business Video Online (July 29, 2014) Nigerian authorities have shut and quarantined a Lagos hospital where a Liberian man died of the Ebola virus, the first recorded case of the highly-infectious disease in Africa's most populous economy. David Pollard reports Video provided by Reuters
Powered by NewsLook.com
Running 5 Minutes A Day Might Add Years To Your Life

Running 5 Minutes A Day Might Add Years To Your Life

Newsy (July 29, 2014) According to a new study, just five minutes of running or jogging a day could add years to your life. Video provided by Newsy
Powered by NewsLook.com
Ebola Outbreak Poses Little Threat To U.S.: CDC

Ebola Outbreak Poses Little Threat To U.S.: CDC

Newsy (July 29, 2014) The Ebola outbreak in West Africa poses little threat to Americans, according to officials with the Centers for Disease Control and Prevention. Video provided by Newsy
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