Research explains mechanism at work in tumor

Feb 22, 2010 by Roberta Friedman

(PhysOrg.com) -- Researchers at the School of Medicine have a new handle on a control switch in cell division that gets stuck on overdrive in some cancers.

Researchers at the School of Medicine have a new handle on a control switch in cell division that gets stuck on overdrive in some cancers.

These new details on a , called UTX, show that it acts on histones—the protein clothespins that keep DNA strands coiled neatly and quietly within the nucleus of cells. The Stanford team, led by Howard Chang, MD, PhD, associate professor of dermatology, found that UTX rubs off chemical marks on certain histones that allow genes to activate and tell cells not to divide.

Unfortunately, is unwanted in cancers, and many instances are associated with mutations in UTX.

“UTX influences hundreds of genes, and some of these are the best-known tumor suppressors,” said Chang, a member of Stanford’s Cancer Center and an early career scientist for the Howard Hughes Medical Institute. In many instances, he said, “it’s what controls the decision of a cell to divide.”

UTX plucks off methyl groups at key control points for genes; that molecular action slams the brakes on cell division. A gene that prevents cancers from growing is called a tumor suppressor, by definition. And UTX is one that controls other tumor suppressors. Its importance is hinted at by the fact that it is present in the most primitive worm, through the mammalian line, to people.

Chang, the senior author of the research published online Feb. 1 in Genes and Development, had collaborated with Harvard researchers to discover UTX in 2007. Developmental biologists have since gathered clues about UTX, and the new study by Chang’s team shows an expanded role for the protein.

The findings show that UTX governs a set of tumor suppressor molecules, called RB binding proteins, that force a cell to stop dividing and then specialize to take on a particular role. do not specialize, but just keep on dividing.

“UTX bound directly to multiple genes that encode proteins that … function in the RB pathway,” the scientists noted in the study. “It makes the connection between several important players,” Chang said.

Some human leukemias and lymphomas result in decreased levels of UTX. In breast cancer, low UTX activity was predictive of patient death, the researchers found. Although UTX would not be a strong enough biomarker to predict cancer response in a particular patient, Chang cautioned, he believes that it is a root cause in many individual cancers. Already, other cancer researchers have identified mutations of UTX in certain human tumors. Chang’s study provides the first explanation of why UTX mutations can lead to cancer.

“People search for mutations in patient samples,” Chang said, “If they see mutant UTX over and over, that implies it’s important. This is definitely one of the drivers.”

Graduate student Jordon Wang is the lead author of the study. Other collaborators include Stanford postdoctoral scholar Miao-Chih Tsai, and researchers at Children’s Hospital Boston, Harvard Medical School and University of Manchester, U.K. The research was funded by the California Institute for Regenerative Medicine, the National Cancer Institute and the American Society.

Explore further: Survival differences seen for advanced-stage laryngeal cancer

add to favorites email to friend print save as pdf

Related Stories

Getting down to cancer basics

Mar 29, 2009

Researchers have identified a new cancer gene - one that is common to many cancers and affects the most basic regulation of our genes. The new example - a gene on the X chromosome called UTX - is found in 10% of cases of ...

New technique creates cancer stem cells

Apr 09, 2008

With a bit of genetic trickery, researchers at the Stanford University School of Medicine have turned normal skin cells into cancer stem cells, a step that will make these naturally rare cells easier to study.

New suppressor of common liver cancer

Dec 15, 2009

Tumor suppressor genes make proteins that help control cell growth. Mutations in these genes that generate nonfunctional proteins can contribute to tumor development and progression. One of the most well-known tumor suppressor ...

Recommended for you

Survival differences seen for advanced-stage laryngeal cancer

10 hours ago

The five-year survival rate for advanced-stage laryngeal cancer was higher than national levels in a small study at a single academic center performing a high rate of surgical therapy, including a total laryngectomy (removal ...

Gene test aids cancer profile

19 hours ago

The first round of chemotherapy did little to suppress Ron Bose's leukemia. The second round, with 10 times the dose, knocked the proliferating blast cells down, but only by half.

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.