Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

BRCA1 causes ovarian cancer through indirect, biochemical route

30.03.2005


Findings by USC researchers provide new potential options for prevention, therapy



Mutated BRCA1 genes cause ovarian cancer indirectly, by interfering with the biochemical signals one ovarian cell sends to another, according to a team of researchers led by scientists at the USC/Norris Comprehensive Cancer Center and the Keck School of Medicine of the University of Southern California. Their work is being published in the March 29 issue of the journal Current Biology.

"Before, we thought this gene was a classical tumor suppressor," says Louis Dubeau, professor of pathology at the Keck School and principal investigator on the paper. If that were the case, it would mean that mutation of the gene would allow the cell it’s in to grow out of control and create a tumor. Instead, Dubeau notes, "What we’ve shown is that the gene actually acts indirectly, that it disrupts interactions between different cell types."


The well-known breast cancer gene, BRCA1, not only gives carriers of its mutated form a four in five chance of developing breast cancer, it also confers a 40 percent risk of developing ovarian cancer by the age of 70. How that risk is imparted, however, had been harder to pin down.

"We’ve known for a long time that ovarian cancer is associated with ovulation, in that women who have regular menstrual cycles through their life without interruption by pregnancy or oral contraceptive use are at highest risk for developing sporadic ovarian cancer," Dubeau explains. "So we had some clues that the cells that control the menstrual cycle-the ovarian granulosa cells-have an influence on ovarian cancer."

But how? Was that influence direct, or indirect? Dubeau eventually got a handle on the problem by looking at ovarian cancer rates in genetically modified mice created in collaboration with Robert Maxson, Keck School professor of biochemistry and molecular biology and director of the mouse core facility at the USC/Norris Cancer Center. "The whole project was based on creating a mouse that lacks BRCA1 in only its granulosa cells," Dubeau says. "This collaboration was essential to the project’s success."

What Dubeau and his colleagues found was that while mutating the BRCA1 gene in granulosa cells did indeed give rise to ovarian tumors, those tumors did not arise in granulosa cells. Instead, when the tumor cells were analyzed, they were found to be epithelial cells very similar to those found in human ovarian cancers, with perfectly intact, functioning copies of the BRCA1 gene.

"What this says is that the cells that control the menstrual cycle, the ovarian granulosa cells, also control ovarian tumor development, but from a distance," Dubeau explains. The most likely scenario, he says, is that the granulosa cells normally give off a chemical signal that stops the epithelial cells from growing out of control. When that chemical signal disappears or is muted by a mutation in the BRCA1 gene, the epithelial cells don’t get the message, and keep on growing and dividing. The result: ovarian cancer.

This finding is actually good news for scientists and physicians trying to figure out new ways to treat ovarian cancer. If the cancer had arisen in the same cells that had the BRCA1 mutation, the only way to interfere would be to correct the mutation. In this case, however, there’s a mediator-a biochemical of some sort-that scientists might be able to replace in people with identified BRCA1 mutations, making their risk of ovarian cancer drop precipitously.

In addition, once the chemical messenger that’s affected has been identified, it will be much easier to diagnose a predisposition to ovarian cancer or pinpoint just who is at risk, simply by measuring the chemical’s levels.

"The consequence of this finding," Dubeau says, "is that ovarian cancer is the result of some biochemical problem that may be correctable or preventable. That’s what makes this finding so exciting."

Dubeau points out that women with BRCA1 mutations are also predisposed to cancers of the fallopian tubes, and that the mice with mutated BRCA1 genes in their granulosa cells developed tumors there as well. "This not only underscores the relevance of our mouse model to human cancer," Dubeau notes, "But also strongly supports a theory we have formulated about the site of origin of ovarian cancers."

Sarah Huoh | EurekAlert!
Further information:
http://www.usc.edu

More articles from Life Sciences:

nachricht Bacteria as pacemaker for the intestine
22.11.2017 | Christian-Albrechts-Universität zu Kiel

nachricht Researchers identify how bacterium survives in oxygen-poor environments
22.11.2017 | Columbia University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Corporate coworking as a driver of innovation

22.11.2017 | Business and Finance

PPPL scientists deliver new high-resolution diagnostic to national laser facility

22.11.2017 | Physics and Astronomy

Quantum optics allows us to abandon expensive lasers in spectroscopy

22.11.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>