Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

La Jolla Institute discovers novel tumor suppressor

04.08.2009
Finding could lead to new therapies for myeloproliferative diseases and some blood cancers

La Jolla Institute for Allergy & Immunology researchers studying an enzyme believed to play a role in allergy onset, instead have discovered its previously unknown role as a tumor suppressor that may be important in myeloproliferative diseases and some types of lymphoma and leukemia.

Myeloproliferative diseases are a group of disorders characterized by an overproduction of blood cells by the bone marrow and include chronic myeloid leukemia. Lymphoma and leukemia are cancers of the blood.

"PLC-beta 3 is an enzyme, but the function we found was a completely different function that no one knew it had -- as a tumor suppressor," said the La Jolla Institute's Toshiaki Kawakami, M.D., Ph.D., who led the research team. The study, conducted in animal models, could eventually lead to the development of new therapies directed towards controlling this newly discovered cellular mechanism.

Tony Hunter, Ph.D., director of the Salk Institute Cancer Center and a professor in Salk's Molecular and Cell Biology Laboratory, called the finding an "important" step in advancing understanding of blood cancers. "It's very interesting that this molecule acts in this way independently of its enzyme activity," he said. "It's quite an unexpected finding and it definitely has the potential for helping the scientific community understand the mechanisms leading to some types of leukemia."

The findings are being published online today in the journal Cancer Cell in a paper entitled "Tumor Suppression by Phospholipase C- 3 via SHP-1-Mediated Dephosphorylation of STAT5." Researchers from UC San Diego Cancer Center, University of Alabama and the University of Western Ontario also contributed to the study.

Dr. Kawakami said he and his research team got their first inkling of something unexpected fairly early on in their experiments. "We wanted to better understand the PLC-beta 3 enzyme's possible role as a signaling pathway in asthma and other allergic diseases, so we began working with mice genetically engineered not to have that enzyme," he said. "We noticed that these mice developed a strange phenotype – myeloproliferation and a variety of tumors including lymphomas and some carcinomas."

Dr. Kawakami said this surprising occurrence suggested that PLC-beta 3 acted as a safeguard that inhibited the development of a variety of tumors. He and his team set out to investigate further, choosing to focus specifically on myeloproliferative disease because almost all of the mice with a defective PLC-beta 3 gene eventually developed severe myeloproliferative disease.

The team determined that tumor production hinged on the PLC-beta 3's ability to block the action of STAT5, a transcription factor protein than can switch on many genes known to control cell proliferation, survival and, in the case of blood stem cells, to promote the development of myeloid cells. Myeloproliferative diseases develop when myeloid cells -- which make certain types of white blood cells—become overactive. "In the absence of the PLC-beta 3 protein, STAT5 goes into a state of constant activation, causing the development of abnormal myeloid cells," said Dr. Kawakami. The abnormal cells, which are essentially tumor cells, become overactive and produce too many blood cells leading to myeloproliferative disease, he explained.

The researchers also tested the finding by introducing an inactive form of STAT5 in PLC-beta 3 deficient mice. "This suppressed myeloproliferative disease in these mice," Dr. Kawakami continued.

Dr. Kawakami said his research team got similar results in tests of human cells from people with Burkitt's lymphoma, an aggressive type of B-cell lymphoma that occurs most often in children and young adults. "Some Burkitt's lymphoma cells have very little PLC-beta 3 expression and have very high levels of STAT5 activity, which is similar to our findings in myeloproliferative disease," he said. "We also have done human cell testing in some other lymphomas and leukemias -- including myeloid leukemia -- indicating that these diseases also use this mechanism (low expression of PLC-beta 3 and high STAT5 activity)."

Dr. Kawakami added that much work still needs to be done. "Our findings need to be explored in other tumors. And, of course, its application in human disease needs further study. But we hope other researchers will be encouraged by our work and that it will prompt not only further analysis of this mechanism's role in various diseases, but attempts to develop drugs that would augment PLC-beta 3 in target cells."

About La Jolla Institute

Founded in 1988, the La Jolla Institute for Allergy & Immunology is a biomedical research nonprofit focused on improving human health through increased understanding of the immune system. Its scientists carry out research seeking new knowledge leading to the prevention of disease through vaccines and the treatment and cure of infectious diseases, cancer and autoimmune diseases such as rheumatoid arthritis, type 1 (juvenile) diabetes, Crohn's disease and asthma. La Jolla Institute's research staff includes more than 100 Ph.D.s and M.D.s.

Bonnie Ward | EurekAlert!
Further information:
http://www.liai.org

More articles from Life Sciences:

nachricht Two Group A Streptococcus genes linked to 'flesh-eating' bacterial infections
25.09.2017 | University of Maryland

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: LaserTAB: More efficient and precise contacts thanks to human-robot collaboration

At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.

Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Fraunhofer ISE Pushes World Record for Multicrystalline Silicon Solar Cells to 22.3 Percent

25.09.2017 | Power and Electrical Engineering

Usher syndrome: Gene therapy restores hearing and balance

25.09.2017 | Health and Medicine

An international team of physicists a coherent amplification effect in laser excited dielectrics

25.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>