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 Closing the carbon loop
08.12.2016 | University of Pittsburgh

nachricht Newly discovered bacteria-binding protein in the intestine
08.12.2016 | University of Gothenburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Closing the carbon loop

08.12.2016 | Life Sciences

Applicability of dynamic facilitation theory to binary hard disk systems

08.12.2016 | Physics and Astronomy

Scientists track chemical and structural evolution of catalytic nanoparticles in 3-D

08.12.2016 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>