Featured Research

from universities, journals, and other organizations

Targeting Mutant B-Raf Protein Reduces Melanoma Development

Date:
May 31, 2005
Source:
Penn State College Of Medicine
Summary:
Researchers at Penn State College of Medicine have identified the mechanism by which the most mutated gene in melanoma, called v599EB-Raf, aids melanoma tumor development demonstrating its importance as a therapeutic target.

HERSHEY, PA -- Researchers at Penn State College of Medicine have identified the mechanism by which the most mutated gene in melanoma, called v599EB-Raf, aids melanoma tumor development demonstrating its importance as a therapeutic target.

"Our studies suggest that using therapies to target and inhibit the function of mutant v599EB-Raf protein could prevent the spread of melanoma and halt tumor growth for those melanomas containing the B-Raf mutation," said Gavin P. Robertson, Ph.D., assistant professor of pharmacology, pathology, and dermatology, Penn State College of Medicine, Penn State Milton S. Hershey Medical Center. "With cases of melanoma increasing at about 4 percent per year and no effective treatments available for advanced-stage disease, it's imperative that we continue to look for important proteins that could be targeted therapeutically. Studies like this one that identify how inhibiting important melanoma regulating proteins reduce melanoma development will lead to a better understanding of the disease, and thus, the development of more effective long-term treatment options for patients."

The study, titled "Mutant V599EB-Raf Regulates Growth and Vascular Development of Malignant Melanoma Tumors," appeared in the March 15, 2005, issue of Cancer Research.

The job of normal non-mutated B-Raf is to relay signals from the cell membrane, which is the boundary of the cell receiving the signals, to the nucleus, which contains genetic material and controls many of the cell's activities. B-Raf is one member of the chain that relays signals playing an important role in cell signaling. The protein is usually only active when needed to relay signals.

In contrast, mutant B-Raf is active all the time, which disrupts the chain's normal function. Previous studies have shown B-Raf is the most mutated gene in melanomas, present in about 60 percent of human melanomas, but the role mutant B-Raf plays in causing melanoma tumors remained unknown.

Robertson used human melanoma cells, applying siRNA, small interfering ribonucleic acids, or BAY 43-9006, a general Raf inhibitor, to show that lowering mutant B-Raf protein reduced melanoma development.

"Reducing B-Raf activity in melanoma cells before tumors had formed significantly decreased the growth potential of the melanoma cells and, in effect, prevented tumor development," Robertson said. "In contrast, reducing B-Raf activity in existing tumors in a mouse model did not shrink the tumors but did prevent them from getting bigger. These discoveries are important for the treatment of metastatic melanoma since therapeutically inhibiting mutant B-Raf could prevent growth of existing tumors and more importantly prevent development of metastatic tumors at secondary sites."

The study shows that in existing melanoma tumors, inhibiting V599EB-Raf activity reduced vascular development, which is essential for tumor growth. Without vascular support the tumors remained the same size. This process occurs by reducing the secretion of VEGF, a factor downstream of B-Raf promoting vascular development, from melanoma cells.

"Because the tumors remained the same size, siRNA or BAY 43-9006 would have to be paired with another therapeutic agent to cause the tumors to shrink or disappear," Robertson said.

Of the major types of skin cancer, melanoma is the most metastatic and lethal form. It is currently the seventh most common cancer in the U.S., with about 52,000 cases diagnosed annually. Furthermore, it is the cancer with the second fastest growth rate. In 2004, an American's lifetime risk of developing melanoma was one in 63 and at the current rate of increase will be one in 50 by 2010. As a direct result of a lack of effective therapeutics, the 2005 prognosis for patients in the metastatic stages of the disease remains very poor with average survival ranging from six to 10 months.

In addition to Robertson, the study team included: Arati Sharma, Nishit R. Trivedi, Melissa A. Zimmerman and Charles D. Smith, Department of Pharmacology, Penn State College of Medicine, Penn State Milton S. Hershey Medical Center, and David A. Tuveson, University of Pennsylvania.

The research was funded by grants from the Melanoma Research Foundation, Foreman Foundation for Melanoma Research, and Barsumian Trust.


Story Source:

The above story is based on materials provided by Penn State College Of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

Penn State College Of Medicine. "Targeting Mutant B-Raf Protein Reduces Melanoma Development." ScienceDaily. ScienceDaily, 31 May 2005. <www.sciencedaily.com/releases/2005/05/050528145727.htm>.
Penn State College Of Medicine. (2005, May 31). Targeting Mutant B-Raf Protein Reduces Melanoma Development. ScienceDaily. Retrieved July 24, 2014 from www.sciencedaily.com/releases/2005/05/050528145727.htm
Penn State College Of Medicine. "Targeting Mutant B-Raf Protein Reduces Melanoma Development." ScienceDaily. www.sciencedaily.com/releases/2005/05/050528145727.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

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
Hundreds in Virginia Turn out for a Free Clinic to Manage Health

Hundreds in Virginia Turn out for a Free Clinic to Manage Health

AFP (July 24, 2014) America may be the world’s richest country, but in terms of healthcare, the World Health Organisation ranks it 37th - prompting hundreds in Virginia to turn out for a free clinic run by “Remote Area Medical”. Duration 02:40 Video provided by AFP
Powered by NewsLook.com
Idaho Boy Helps Brother With Disabilities Complete Triathlon

Idaho Boy Helps Brother With Disabilities Complete Triathlon

Newsy (July 23, 2014) An 8-year-old boy helped his younger brother, who has a rare genetic condition that's confined him to a wheelchair, finish a triathlon. 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