Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers identify important function of NF2 tumor suppressor

02.05.2003


Protein plays role in inherited cancer syndrome, may be key to other tumors



A research team based at Massachusetts General Hospital (MGH) has identified a key cellular function of a protein known to be involved in the rare genetic disorder neurofibromatosis type 2 (NF2). The protein, called merlin, plays a key role in cell-to-cell communication and may be involved in other types of cancer. The discovery also may support the theory that some tumors are destined to spread or metastasize from the outset, rather than gaining the ability to spread as they develop. The report appears in the May 1, 2003, issue of Genes & Development.

NF2 is a rare inherited disorder characterized by multiple tumors of the spine and brain. The NF2 gene was discovered in 1993 by researchers from MGH and elsewhere. At the time of its discovery it was apparent that the NF2 gene was a tumor suppressor, but its exact function was unclear. The protein encoded by the NF2 gene, given the name merlin, was found at the interface of the cell membrane with the cytoskeleton, a network of filaments that supports the cell.


"Since merlin is a tumor suppressor whose loss of function leads to tumor development, it is absolutely critical to define what happens when this function is lost," says Andrea McClatchey, PhD, of the MGH Cancer Center, the senior author of the current report. "Our objective was to define the primary cellular and molecular consequences of that loss of function."

McClatchey and her colleagues had previously developed a strain of mice genetically engineered to lack normal Nf2 genes. This animal model allowed them to identify the gene’s function by comparing cells from the Nf2-mutant mice with cells of the same type from normal mice. They found that, while the Nf2-deficient cells looked normal and multiplied normally, they did not stop multiplying when they came into contact with other cells in the culture dish. The normal cells stopped growing when they filled the culture dish, but the Nf2-deficient cells kept piling up on each other, suggesting that the cells could not sense they were touching other cells.

Followup experiments showed that the Nf2-deficient cells were lacking key cellular structures called adherens junctions. Located in the cell membrane, adherens junctions connect adjacent cells and are known to play a role in cell-to-cell communications. The researchers found merlin in the adherens junctions of normal cells and discovered that adding normal merlin protein to cultures of Nf2-deficient cells restored both the formation of adherens junctions and contact-dependent growth inhibition.

"Our study suggests that, through its link to the cellular cytoskeleton, merlin normally organizes the structure that facilitates cell-to-cell communication – the adherens junction," says McClatchey, who is an assistant professor of Pathology at Harvard Medical School. "Loss of junction integrity has been linked to both tumor development and tumor invasion, providing an explanation for the striking development of metastatic cancer in Nf2-mutant mice,"

McClatchey notes that NF2 mutations in humans have also been associated with mesothelioma, a highly malignant type of lung cancer caused by asbestos exposure, and may be associated with other forms of cancer. She believes that future research may show that NF2 mutations induced by environmental or other factors could play a broader role in cancer development and that strategies to restore or enhance merlin function may lead to potential therapies for NF2-associated cancer.

The current finding also echoes other recent studies that may change some fundamental theories about cancer development. It has been thought that as tumors develop and cells keep mutating, some of them acquire characteristics that enable them to spread beyond the original site, essentially to become malignant. However, some recent studies that examine which genes are expressed or turned on in tumor cells suggest that the capacity to metastasize is inherent from the original tumor-inducing mutation.

"Given that loss of adherens junctions has been linked to both tumor initiation and tumor metastasis," says McClatchey, "loss of NF2 may be an example of an event that both starts a tumor and confers metastatic potential."



McClatchey’s co-authors are first author Dominique Lallemand, PhD, Marcello Curto, MD, PhD, and Ichiko Saotome all of the MGH Cancer Center; and Marco Giovannini, MD, PhD, of INSERM (French National Institute for Health and Medical Research) in Paris. The research was supported by grants from the Amerian Cancer Society, the Department of Defense Neurofibromatosis Program, Ligue Contre le Cancer (France), the National Neurofibromatosis Foundation, and the Association pour la Recherche Contre le Cancer (French Association for Cancer Research).


Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $350 million and major research centers in AIDS, cardiovascular research, cancer, cutaneous biology, neurodegenerative disorders, transplantation biology and photomedicine. In 1994, MGH and BWH joined to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups and nonacute and home health services.

Susan McGreevey | EurekAlert!
Further information:
http://www.mgh.harvard.edu/

More articles from Life Sciences:

nachricht A room with a view - or how cultural differences matter in room size perception
25.04.2017 | Max-Planck-Institut für biologische Kybernetik

nachricht Studying a catalyst for blood cancers
25.04.2017 | University of Miami Miller School of Medicine

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Early organic carbon got deep burial in mantle

25.04.2017 | Earth Sciences

A room with a view - or how cultural differences matter in room size perception

25.04.2017 | Life Sciences

Warm winds: New insight into what weakens Antarctic ice shelves

25.04.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>