Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Loss of Tumor Supressor Gene Essential in Transforming Benign Nerve Tumors into Cancers

14.10.2009
Researchers at UCLA’s Jonsson Comprehensive Cancer Center showed for the first time that the loss or decreased expression of the tumor suppressor gene PTEN plays a central role in the malignant transformation of benign nerve tumors called neurofibromas into a malignant and extremely deadly form of sarcoma.

The work, a collaboration between the Institute for Molecular Medicine, the Department of Molecular and Medical Pharmacology and the cancer center’s Sarcoma Program, could lead to the development of new therapies that target the cell signaling pathway regulated by PTEN.

A novel mouse model of neurofibromatosis type 1 (NF1) developed at UCLA first illustrated the importance of PTEN tumor suppressor in malignant transformation and this finding was validated in human malignant peripheral nerve sheath tumors, the deadly sarcomas.

The study will be published this week in the early online edition of the peer-reviewed journal Proceedings of the National Academy of Sciences.

“The loss of expression of PTEN in the human sarcomas we studied mirrored the loss of PTEN in mice, and we anticipate being able to target this pathway abnormality for the development of new methods of diagnosis and treatment” said Dr. Fritz Eilber, director of the Sarcoma Program and an assistant professor of surgical oncology. “Within the sarcoma world, malignant peripheral nerve sheath tumors are one of the most lethal sub-types, so this is a significant finding and may lead to new and more effective treatments.”

NF1 is one of the most common genetically inherited disorders, with an incidence of about 1 in every 2,500 births, said, Dr. Hong Wu, associate director of the molecular medicine institute, a Jonsson Cancer Center researcher and senior author of the study.

“Patients with NF1 have an about 10 percent lifetime risk of developing this lethal sarcoma sub-type,” Wu said.

The study also showed that Positron Emission Tomography (PET) scanning with the glucose analogue FDG - both in the mice and in humans - is a highly accurate way to distinguish between the benign tumors and the malignant ones, indicating that this non-invasive imaging technology is valuable in assessing therapeutic response to new treatments.

Wu created the mouse model with two of her graduate students, Caroline Gregorian and Jonathan Nakashima, co-first authors of this paper. It was created by altering two cell signaling pathways that are commonly activated in peripheral and central nervous system cancers, the RAS/RAF/MAPK & PTEN/P13K/AKT pathways, known to regulate cell proliferation, survival and differentiation.

“When we began to generate mouse models to mimic different human cancers, we usually did gene-based analysis to see the relevance of a specific gene in the development of the cancer,” Wu said. “But we realize that sometimes targeting the cell signaling pathways that organize and instruct cells to function, both for normal functions of our body and also in abnormal ways in disease, are more important and informative than the individual gene”

The mouse model developed benign neurofibromas, but then progressed to the deadly sub-type of sarcoma. The neurofibromas had half the normal levels of PTEN and the sarcomas had a complete loss of PTEN. Since PTEN is an important factor in suppressing cells from becoming malignant, this could provide an explanation for the sequence of the normal cells transforming into benign neurofibromas that could then transform into cancer.

Wondering if this was also the case in people, Dr. Wu collaborated with Eilber and pathologist Dr. Sarah Dry, director of the Institute of Molecular Medicine’s Pathway Pathology Center, and a multidisciplinary team of physician-scientists to determine if people with this sarcoma sub-type also had little or no PTEN.

“This type of collaboration is the hallmark of the work at the Jonsson Cancer Center and molecular medicine institute - translating discoveries in a basic science lab into discoveries in patients,” Wu said.

Currently, there are no effective treatments to prevent the benign NF1 tumors from transforming into cancer. The genetically engineered mouse model will be used to screen drugs that may be able to target the signaling pathway regulated by PTEN, to block signals that instruct the cells to change from a benign state to a malignant one, providing treatment options for patients with the deadly form of cancer.

“I think these findings will help us provide a better diagnosis that can determine if the neurofibroma is becoming a malignant tumor or not,” Eilber said. “But more importantly, the loss of the PTEN and its associated signaling pathways gives us targets for therapy and it may lay the foundation for treatment in other sarcomas as well.”

Also involved in the research were Dr. Paul Mischel, Dr. Simin Liu, Dr. Phioanh Leia Nghiemphu, Dr. Greg Lawson, Dr. Michael Sofroniew and Dr. Michael Phelps, director of the molecular medicine institute and creator of the PET scanner

The study was funded by the United States Department of Health and Human Services, the National Cancer Institute, the National Institutes of Health, UCLA’s Jonsson Comprehensive Cancer Center, the American Cancer Society, the Brain Tumor Society, the Henry Singleton Brain Cancer Research Program and the James S. McDonnell Foundation.

UCLA's Jonsson Comprehensive Cancer Center has more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2009, the Jonsson Cancer Center was named among the top 12 cancer centers nationwide by U.S. News & World Report, a ranking it has held for 10 consecutive years.

Kim Irwin | Newswise Science News
Further information:
http://www.cancer.ucla.edu

More articles from Life Sciences:

nachricht Are there sustainable solutions in dealing with dwindling phosphorus resources?
16.10.2017 | Leibniz-Institut für Nutzierbiologie (FBN)

nachricht Strange undertakings: ant queens bury dead to prevent disease
13.10.2017 | Institute of Science and Technology Austria

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

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...

Im Focus: New nanomaterial can extract hydrogen fuel from seawater

Hybrid material converts more sunlight and can weather seawater's harsh conditions

It's possible to produce hydrogen to power fuel cells by extracting the gas from seawater, but the electricity required to do it makes the process costly. UCF...

Im Focus: Small collisions make big impact on Mercury's thin atmosphere

Mercury, our smallest planetary neighbor, has very little to call an atmosphere, but it does have a strange weather pattern: morning micro-meteor showers.

Recent modeling along with previously published results from NASA's MESSENGER spacecraft -- short for Mercury Surface, Space Environment, Geochemistry and...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

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

Conference Week RRR2017 on Renewable Resources from Wet and Rewetted Peatlands

28.09.2017 | Event News

 
Latest News

A single photon reveals quantum entanglement of 16 million atoms

16.10.2017 | Physics and Astronomy

The melting ice makes the sea around Greenland less saline

16.10.2017 | Earth Sciences

On the generation of solar spicules and Alfvenic waves

16.10.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>