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 Transport of molecular motors into cilia
28.03.2017 | Aarhus University

nachricht Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Researchers shoot for success with simulations of laser pulse-material interactions

29.03.2017 | Materials Sciences

Igniting a solar flare in the corona with lower-atmosphere kindling

29.03.2017 | Physics and Astronomy

As sea level rises, much of Honolulu and Waikiki vulnerable to groundwater inundation

29.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>