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 Historical rainfall levels are significant in carbon emissions from soil
30.05.2017 | University of Texas at Austin

nachricht 3D printer inks from the woods
30.05.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: New Method of Characterizing Graphene

Scientists have developed a new method of characterizing graphene’s properties without applying disruptive electrical contacts, allowing them to investigate both the resistance and quantum capacitance of graphene and other two-dimensional materials. Researchers from the Swiss Nanoscience Institute and the University of Basel’s Department of Physics reported their findings in the journal Physical Review Applied.

Graphene consists of a single layer of carbon atoms. It is transparent, harder than diamond and stronger than steel, yet flexible, and a significantly better...

Im Focus: Strathclyde-led research develops world's highest gain high-power laser amplifier

The world's highest gain high power laser amplifier - by many orders of magnitude - has been developed in research led at the University of Strathclyde.

The researchers demonstrated the feasibility of using plasma to amplify short laser pulses of picojoule-level energy up to 100 millijoules, which is a 'gain'...

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

3D printer inks from the woods

30.05.2017 | Life Sciences

How circadian clocks communicate with each other

30.05.2017 | Life Sciences

Graphene and quantum dots put in motion a CMOS-integrated camera that can see the invisible

30.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>