Featured Research

from universities, journals, and other organizations

Tracing The Pathways Of Neurofibromatosis: Researchers Find Genetic Flaw Starts Biochemical Domino Effect

Date:
January 19, 2007
Source:
Rice University
Summary:
New research into the mechanisms of neurofibromatosis finds that flaws in the gene Nf1 can lead to a biochemical domino effect that results in tumors. The research, which appears in the January 10 issue of the Journal of Neuroscience, seeks to identify the biochemical pathway responsible for tumors in people with the genetic disorder. Researchers built their case based on evidence from dozens of painstaking experiments on genetically engineered fruit flies.

Michael Stern's latest research into the formation of neurofibromatosis tumors reads something like a federal racketeering indictment, except that Stern's tracing proteins instead of laundered money, and he's looking not at offshore accounts but at biochemical paths of cause and effect.

The research, which appears in the Jan. 10 issue of the Journal of Neuroscience, seeks to find the biochemical pathway that's responsible for tumors in people with the genetic disorder neurofibromatosis. Stern built his case much like a prosecutor, compiling evidence from dozens of painstaking experiments on mutant fruit flies, each with a specific genetic flaw that testified to the power of one or more proteins involved.

Neurofibromatosis is characterized by the formation of tumors of peripheral nerve cells. Scientists know the disease is caused by defects in a gene called Nf1, but they have yet to find out precisely how the defective genes cause tumors to form.

"Our results suggest that having a defect in Nf1 begins a kind of biochemical domino effect that eventually leads to tumor growth," said Stern, professor of biochemistry and cell biology.

Stern's research group used fruit flies for several reasons: the insect's genome has been sequenced; it takes only two weeks to grow an new generation of fruit flies; and scientists know which fruit fly genes are analogous to the human genes associated with neurofibromatosis.

In preparing for its experiments, Stern's group knew that Nf1 encodes a protein called neurofibromin that inhibits the effect of a second protein called Ras, which is known to promote nerve cell growth. They also knew that a third protein called PI3K was recently reported to be hyperactivated in mice that had defective Nf1 genes, and they knew that PI3K requires the activity of a fourth protein called Akt, to carry out its tasks.

In their experiments, they created more than two dozen mutant strains of fruit flies, including varieties that were either missing the genes to make one of the four proteins or were encoded to overexpress, or make extra amounts of, one of the four. Some mutants were designed to carry more than one defective trait.

Nerves from each mutant strain were examined. By comparing the mutant strains -- each with a specific defect or set of defects -- they buillt a case that the absence of neurofibromin allows Ras, PI3K and Akt to work in concert to inhibit a regulatory group of proteins called 'forkhead box O,' or FOXO. FOXO proteins are key players in regulating the genes responsible for programmed cell death and DNA repair -- two common culprits in cancer.

"Our results raise the possibility that neurofibroma formation in individuals with neurofibromatosis might result in part from a Ras-PI3K-Akt-dependent inhibition of FOXO," Stern said.

Stern said the project required an enormous amount of work in the lab, and it wouldn't have been possible without the dedication and motivation of research technician Willliam Lavery, the paper's first author.

"Will displayed terrific leadership on this project," Stern said.

Stern and Lavery's co-authors include research technician Michelle Wells, postdoctoral research assistant Veronica Hall, graduate student James Yager and undergraduate Alex Rottgers.

The research is supported by the Department of Defense Neurofibromatosis Research Program.


Story Source:

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


Cite This Page:

Rice University. "Tracing The Pathways Of Neurofibromatosis: Researchers Find Genetic Flaw Starts Biochemical Domino Effect." ScienceDaily. ScienceDaily, 19 January 2007. <www.sciencedaily.com/releases/2007/01/070118130008.htm>.
Rice University. (2007, January 19). Tracing The Pathways Of Neurofibromatosis: Researchers Find Genetic Flaw Starts Biochemical Domino Effect. ScienceDaily. Retrieved September 20, 2014 from www.sciencedaily.com/releases/2007/01/070118130008.htm
Rice University. "Tracing The Pathways Of Neurofibromatosis: Researchers Find Genetic Flaw Starts Biochemical Domino Effect." ScienceDaily. www.sciencedaily.com/releases/2007/01/070118130008.htm (accessed September 20, 2014).

Share This



More Health & Medicine News

Saturday, September 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Sierra Leone's Nationwide Ebola Curfew Underway

Sierra Leone's Nationwide Ebola Curfew Underway

Newsy (Sep. 20, 2014) Sierra Leone is locked down as aid workers and volunteers look for new cases of Ebola. Video provided by Newsy
Powered by NewsLook.com
Changes Found In Brain After One Dose Of Antidepressants

Changes Found In Brain After One Dose Of Antidepressants

Newsy (Sep. 19, 2014) A study suggest antidepressants can kick in much sooner than previously thought. Video provided by Newsy
Powered by NewsLook.com
Could Grief Affect The Immune Systems Of Senior Citizens?

Could Grief Affect The Immune Systems Of Senior Citizens?

Newsy (Sep. 19, 2014) The study found elderly people are much more likely to become susceptible to infection than younger adults going though a similar situation. Video provided by Newsy
Powered by NewsLook.com
Jury Delivers Verdict in Salmonella Trial

Jury Delivers Verdict in Salmonella Trial

AP (Sep. 19, 2014) A federal jury has convicted three people in connection with an outbreak of salmonella poisoning five years ago that sickened hundreds of people and was linked to a number of deaths. (Sept. 19) Video provided by AP
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