Featured Research

from universities, journals, and other organizations

New RNA interference technique finds seven genes for head and neck cancer

Date:
February 16, 2014
Source:
Rockefeller University
Summary:
In the hunt for genetic mutations that cause cancer, there is a lot of white noise. So although genetic sequencing has identified hundreds of genetic alterations linked to tumors, it's still an enormous challenge to figure out which ones are actually responsible for the growth and metastasis of cancer. Scientists have now created a new technique that can weed out that noise -- eliminating the random bystander genes and identifying the ones that are critical for cancer. Applying their technique to head and neck cancers, they've discovered seven new tumor-suppressor genes whose role in cancer was previously unknown.

Interfering with cancer. A section of a head and neck tumor — red and green markers show the proliferation of cancer stem cells — that formed when one of several newly characterized genes, Myh9, was suppressed. A recently developed genetic screening technique using RNA interference identified Myh9’s protein, myosin IIa, as playing an important role in tumor suppression.
Credit: Image courtesy of Rockefeller University

In the hunt for genetic mutations that cause cancer, there is a lot of white noise. So although genetic sequencing has identified hundreds of genetic alterations linked to tumors, it's still an enormous challenge to figure out which ones are actually responsible for the growth and metastasis of cancer. Scientists in Rockefeller's Laboratory of Mammalian Cell Biology and Development have created a new technique that can weed out that noise -- eliminating the random bystander genes and identifying the ones that are critical for cancer. Applying their technique to head and neck cancers, they've discovered seven new tumor-suppressor genes whose role in cancer was previously unknown.

The new technique, which the lab recently applied to a screen for skin tumor genes, is particularly useful because it takes a fraction of the resources and much less time than the traditional method for determining gene function -- breeding genetically modified animals to study the impact of missing genes.

"Using knockout mice, which are model organisms bred to have a particular gene missing, is not feasible when there are 800 potential head and neck cancer genes to sort through," says Daniel Schramek, a postdoctoral fellow in the lab, which is headed by Rebecca C. Lancefield Professor Elaine Fuchs. "It can take about two years per gene. Our method can assess about 300 genes in a single mouse, in as little as five weeks."

The researchers made use of RNA interference, a natural process whereby RNA molecules inhibit gene expression. They took short pieces of RNA which are able to turn off the function of specific genes, attached them to highly concentrated viruses, and then, using ultrasound to guide the needle without damaging surrounding tissue, they injected the viruses into the sacs of mouse embryos.

"The virus is absorbed and integrated into the chromosomes of the single layer of surface cells that cover the tiny embryo," explains Fuchs. "As the embryo develops, this layer of cells becomes the skin, mammary glands and oral tissue, enabling us to efficiently, selectively and quickly eliminate the expression of any desired gene in these tissues. The non-invasive method avoids triggering a wound or inflammatory response that is typically associated with conventional methods to knockdown a gene in cultured cells and then engraft the cells onto a mouse."

When the mice grew, the researchers determined which genes, when turned off, were promoting tumor growth, and what they found was surprising.

"Among the seven novel tumor suppressor genes we found, our strongest hit was Myh9, which codes for the protein myosin IIa, a motor protein with well-known function in cell structure and cell migration," says Schramek. "Through further functional studies we found that myosin IIa is also required for activation of the main guardian of the genome -- a tumor suppressor protein called p53."

The lab showed that when the myosin IIa gene was mutated, p53 was not able to build up in the cell nucleus, and chaos ensued: genes responsible for repairing damaged cells and killing off tumor cells were not activated, and invasive carcinomas spread within three months.

The researchers devised a strategy to reactivate p53 in these cells, and showed in vitro that tumor suppression was restored. "Head and neck cancers are the sixth most deadly type of cancer worldwide. Interestingly, Myh9 is also mutated in human head and neck cancers, and low expression of myosin IIa correlates with poor prognosis for the patient," says Fuchs. The group hopes to examine the effect in clinical trials in the future, and plans to look at the function of the other six genes their study identified.

"We've demonstrated that this method of RNA interference is highly useful in the rapid discovery, validation and characterization of tumor suppressor genes that might otherwise be missed in a genetic screen," says Schramek. "It can be applied to many kinds of cancers, such as breast and lung."


Story Source:

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


Journal Reference:

  1. D. Schramek, A. Sendoel, J. P. Segal, S. Beronja, E. Heller, D. Oristian, B. Reva, E. Fuchs. Direct in Vivo RNAi Screen Unveils Myosin IIa as a Tumor Suppressor of Squamous Cell Carcinomas. Science, 2014; 343 (6168): 309 DOI: 10.1126/science.1248627

Cite This Page:

Rockefeller University. "New RNA interference technique finds seven genes for head and neck cancer." ScienceDaily. ScienceDaily, 16 February 2014. <www.sciencedaily.com/releases/2014/02/140216182016.htm>.
Rockefeller University. (2014, February 16). New RNA interference technique finds seven genes for head and neck cancer. ScienceDaily. Retrieved April 24, 2014 from www.sciencedaily.com/releases/2014/02/140216182016.htm
Rockefeller University. "New RNA interference technique finds seven genes for head and neck cancer." ScienceDaily. www.sciencedaily.com/releases/2014/02/140216182016.htm (accessed April 24, 2014).

Share This



More Health & Medicine News

Thursday, April 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deadly Fungus Killing Bats, Spreading in US

Deadly Fungus Killing Bats, Spreading in US

AP (Apr. 24, 2014) A disease that has killed more than six million cave-dwelling bats in the United States is on the move and wildlife biologists are worried. White Nose Syndrome, discovered in New York in 2006, has now spread to 25 states. (April 24) Video provided by AP
Powered by NewsLook.com
Companies Ramp Up Wellness to Lower Health Costs

Companies Ramp Up Wellness to Lower Health Costs

AP (Apr. 24, 2014) That little voice telling you to exercise, get in shape and get healthy is probably coming from your boss. More companies are beefing up wellness programs to try and cut down their health care costs. (April 24) Video provided by AP
Powered by NewsLook.com
FDA Wants To Ban Sales Of E-Cigarettes To Minors

FDA Wants To Ban Sales Of E-Cigarettes To Minors

Newsy (Apr. 24, 2014) The Food and Drug Administration wants to crack down on the use of e-cigarettes, banning the sale of the product to minors. Video provided by Newsy
Powered by NewsLook.com
Michigan Man Sees Thanks to 'bionic Eye'

Michigan Man Sees Thanks to 'bionic Eye'

AP (Apr. 23, 2014) A legally blind Michigan man is 'seeing something new every day' thanks to a high-tech retinal implant procedure. He's one of the first in the country to receive a 'bionic eye' since the federal government approved the surgery. (April 23) 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