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La Jolla Institute discovers novel tumor suppressor
Date:8/3/2009

g 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 cellsbecome 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 mye
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Contact: Bonnie Ward
contact@liai.org
619-303-3160
La Jolla Institute for Allergy and Immunology
Source:Eurekalert

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