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 Scientists unlock ability to generate new sensory hair cells
22.02.2017 | Brigham and Women's Hospital

nachricht New insights into the information processing of motor neurons
22.02.2017 | Max Planck Florida Institute for Neuroscience

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Microhotplates for a smart gas sensor

22.02.2017 | Power and Electrical Engineering

Scientists unlock ability to generate new sensory hair cells

22.02.2017 | Life Sciences

Prediction: More gas-giants will be found orbiting Sun-like stars

22.02.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>