Cell-enlargement discovery puts new twist on brain tumor research

St. Jude Children's Research Hospital (ALSAC)
Thursday, 13 December 2001

Medical model reveals clues to rare brain disorder

(Memphis, Tennessee – December. 13, 2001) PTEN, a tumor-suppressor gene that when mutated leads to brain tumors and other cancers, causes neurons in the brain to grow larger, not multiply, a recent study shows. This research will help scientists understand the underlying mechanisms of how this tumor-suppressor gene may lead to brain tumor formation.

The study, published in December's Nature Genetics by scientists at St. Jude Children's Research Hospital and Johns Hopkins University School of Medicine, provides researchers with an understanding of PTEN's role in cell-growth regulation and how mutations of this gene cause tumors. The St. Jude scientists, led by Suzanne Baker, Ph.D., created a model system of the tumor suppressor's genetic role.

"Understanding the consequences of PTEN loss may help scientists identify new targets for therapeutics," Baker said.

PTEN loss, most often associated with the aggressive glioblastoma brain tumor, also leads to other cancers, including prostate and endometrial cancers.

"We found that PTEN is critical in regulating how neurons grow in terms of the size of each individual cell," Baker said. "This study gives us new insight into how this gene might function. It was unexpected that a tumor suppressor normally associated with regulating cell division and survival does something different. We hope our follow-up studies, which are designed to understand all subsequent PTEN loss effects, will explain to us the context of its function in tumors."

The study also provides insights into the rare genetic disease Lhermitte-Duclos, in which PTEN is mutated. Lhermitte-Duclos, which affects the cerebellum, is associated with seizures, loss of balance and disruption of other brain functions.

The St. Jude experimental model showed that the disease occurs when a specific class of neurons in the brain loses PTEN and grows larger over time.

"By creating an experimental situation where we can follow this process over time, we're able to understand exactly what went wrong in the human disease," Baker said.

Using their genetic model, Baker's team will study the other cellular effects that occur when PTEN is removed.

"We hope that by doing that, we might be able to counteract a loss of PTEN, which could be an important step in battling the cancers associated with PTEN loss, along with Lhermitte-Duclos disease," Baker added.

St. Jude Children's Research Hospital, in Memphis, Tenn., was founded by the late entertainer Danny Thomas. The hospital is an internationally recognized biomedical research center dedicated to finding cures for catastrophic diseases of childhood. The hospital's work is supported through funds raised by the American Lebanese Syrian Associated Charities (ALSAC). ALSAC covers all costs not covered by insurance for medical treatment rendered at St. Jude Children's Research Hospital. Families without insurance are never asked to pay.

For more information, or to contact St. Jude Children's Research Hospital (ALSAC), see their website at: www.stjude.org