Featured Research

from universities, journals, and other organizations

Novel Tumor Suppressor Discovered

Date:
August 12, 2009
Source:
La Jolla Institute for Allergy and Immunology
Summary:
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.

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.

Related Articles


"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."


Story Source:

The above story is based on materials provided by La Jolla Institute for Allergy and Immunology. Note: Materials may be edited for content and length.


Cite This Page:

La Jolla Institute for Allergy and Immunology. "Novel Tumor Suppressor Discovered." ScienceDaily. ScienceDaily, 12 August 2009. <www.sciencedaily.com/releases/2009/08/090803122719.htm>.
La Jolla Institute for Allergy and Immunology. (2009, August 12). Novel Tumor Suppressor Discovered. ScienceDaily. Retrieved November 24, 2014 from www.sciencedaily.com/releases/2009/08/090803122719.htm
La Jolla Institute for Allergy and Immunology. "Novel Tumor Suppressor Discovered." ScienceDaily. www.sciencedaily.com/releases/2009/08/090803122719.htm (accessed November 24, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Monday, November 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Winter Can Cause Depression — Here's How To Combat It

Winter Can Cause Depression — Here's How To Combat It

Newsy (Nov. 23, 2014) Millions of American suffer from seasonal depression every year. It can lead to adverse health effects, but there are ways to ease symptoms. Video provided by Newsy
Powered by NewsLook.com
Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

AFP (Nov. 23, 2014) The arable district of Kenema in Sierra Leone -- at the centre of the Ebola outbreak in May -- has been under quarantine for three months as the cocoa harvest comes in. Duration: 01:32 Video provided by AFP
Powered by NewsLook.com
Don't Fall For Flu Shot Myths

Don't Fall For Flu Shot Myths

Newsy (Nov. 23, 2014) Misconceptions abound when it comes to your annual flu shot. Medical experts say most people older than 6 months should get the shot. Video provided by Newsy
Powered by NewsLook.com
WFP: Ebola Risks Heightened Among Women Throughout Africa

WFP: Ebola Risks Heightened Among Women Throughout Africa

AFP (Nov. 21, 2014) Having children has always been a frightening prospect in Sierra Leone, the world's most dangerous place to give birth, but Ebola has presented an alarming new threat for expectant mothers. Duration: 00:37 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins