Navigation Links
Loss of tumor supressor gene essential to transforming benign nerve tumors into cancers
Date:10/13/2009

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."


'/>"/>

Contact: Kim Irwin
kirwin@mednet.ucla.edu
310-206-2805
University of California - Los Angeles
Source:Eurekalert

Related biology news :

1. Invasion of the brain tumors
2. Novel 3-D cell culture model shows selective tumor uptake of nanoparticles
3. Bits of junk RNA aid master tumor-suppressor gene
4. Analysis of breast and colon cancer genes finds many areas of differences between tumors
5. Tumor genome analysis unveils new insights into lung cancer
6. Cell response to stress signals predicts tumors in women with common pre-breast cancer
7. Synthetic compound promotes death of lung-cancer cells, tumors
8. MIT: Remote-control nanoparticles deliver drugs directly into tumors
9. New X-ray technique targets terrorists and tumors
10. DNA methylation shown to promote development of colon tumors
11. Gene variation may elevate risk of liver tumor in patients with cirrhosis
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/20/2016)... , Jan. 20, 2016   MedNet Solutions ... the entire spectrum of clinical research, is pleased to ... MedNet,s significant achievements are the result of the company,s ... iMedNet eClinical , it,s comprehensive, easy-to-use and ... --> Key MedNet growth achievements in ...
(Date:1/18/2016)... Jan. 18, 2016  Extenua Inc., a pioneering ... the use and access of ubiquitous on-premise and ... with American Cyber.  ... leading transformational C4ISR and Cyber initiatives in support ... latest proven technology solutions," said Steve Visconti ...
(Date:1/13/2016)... ALBANY, New York , January 13, 2016 /PRNewswire/ ... Transparency Market Research has published a new market report ... Share, Growth, Trends, and Forecast, 2015 - 2023. According to ... mn in 2014 and is anticipated to reach US$1,625.8 ... from 2015 to 2023. In terms of volume, the ...
Breaking Biology News(10 mins):
(Date:2/11/2016)... 11, 2016 Non-profit Consortium Aims to ... to Support Research and Discovery --> ... an ambitious plan to sequence 100,000 individuals. It is intended ... at least 7 of North and East Asian countries. ... phase, the project will focus on creating phased reference genomes ...
(Date:2/11/2016)... , Feb. 11, 2016  Spectra BioPharma Selling Solutions ... that provides biopharma companies the experience, expertise, operational ... deploy outsourced sales teams. Created in concert with ... both the strategic and tactical needs of its ... solutions through both personal and non-personal promotion. ...
(Date:2/11/2016)...   BioInformant announces the February 2016 release ... Opportunities, Tools, and Technologies – Market Size, Segments, Trends, ... The first and only market ... BioInformant has more than a decade of historical information ... stem cell type. This powerful 175 page global strategic ...
(Date:2/10/2016)... Early-career researchers from ... , Uganda and Yemen ... nutrition   Indonesia , Nepal ... Yemen are being honored for their accomplishments in ... celebrated for mentoring young women scientists who are pursuing careers in agriculture, ...
Breaking Biology Technology: