Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

BRCA1 gene found to inhibit two sex hormones, not just one

27.01.2006


Could help explain why women who have mutations in their BRCA1 gene are susceptible to ’hormone-dependent’ cancers including breast, endometrial and cervical cancers



It’s been known that the breast cancer susceptibility gene BRCA1 regulates use of estrogen in breast and other cells, but now researchers at Georgetown University Medical Center have discovered that it also controls activity of a second sex steroid hormone, progesterone.

The findings, conducted in cell culture and in mice and reported by the researchers in the January issue of Molecular Endocrinology, could help explain why women who have mutations in their BRCA1 gene are susceptible to a number of different "hormone-dependent" cancers, including those of the breast, endometriun and cervix.


It also has implications for ordinary cancers that arise because a normal BRCA1 gene is under-expressed, said the study’s principal investigator, Eliot Rosen, MD, PhD, professor of oncology, cell biology, and radiation medicine at the Lombardi Comprehensive Cancer Center.

For example, he says that up to 40 percent of breast tumors are deficient in BRCA1, "and it may be that some patients could benefit not only from an anti-estrogen therapy, like tamoxifen, but also from an anti-progesterone agent.

"We don’t know if that is true yet, of course, but it is certainly worth investigating, given our findings," Rosen said.

The BRCA1 gene and a second gene, BRCA2, were discovered to be breast cancer susceptibility genes in 1994 and 1995, respectively. Women who inherit faulty copies of one of these genes have up to an 80 percent increased risk of developing breast cancer by age 70, and are also more likely to be diagnosed with ovarian cancer.

Rosen and his research team undertook the study to understand why loss of the BRCA1 gene results in cancers in tissues that are dependent on hormones. They focused on the progesterone hormone, in part, because of the observation that women who use hormone replacement therapy that includes both estrogen and progestin (a synthetic form of progesterone) are at greater risk of developing breast cancer than women who use only estrogen replacement.

The use of progesterone in the breast is tightly regulated and is primarily activated when growth in cells is needed, such as during the female menstrual cycle and to support a pregnancy. A cell’s use of progesterone and other such hormones is controlled by specific receptor proteins, located inside cells, which bind on to the hormone. This process activates the receptor, which then migrates to the cell nucleus to stimulate gene expression.

To find out what role BRCA1 played in progesterone receptor signaling, the Lombardi research team conducted a series of experiments. In one set of cell culture studies in the laboratory, they used breast cancer cells that were responsive to progesterone, and then genetically manipulated them to either over or under-express the BRCA1 gene in order to assess the gene’s effect on progesterone receptor signaling.

They also used mice in which the BRCA1 gene was partially deleted, but only in breast tissue. The animals were treated with estrogen, or progesterone, or both, and response of the mammary gland was compared with that of normal mice.

In this way, the researchers concluded that BRCA1 interacts physically with the progesterone receptor, and stops it from activating other genes. It does this even in the absence of the progesterone hormone, and, thus, acts as a strong check on errant growth.

"But in mice deficient in BRCA1, we found that estrogen plus progesterone has a particularly large effect in stimulating the growth of mammary epithelial cells − an effect much greater than the effects of either hormone used alone," Rosen said.

Liz McDonald | EurekAlert!
Further information:
http://www.georgetown.edu

More articles from Life Sciences:

nachricht The birth of a new protein
20.10.2017 | University of Arizona

nachricht Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

Strange but true: Turning a material upside down can sometimes make it softer

20.10.2017 | Materials Sciences

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>