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LI study: Cancer gene has role in stroke

A file photo of a doctor with patient.

A file photo of a doctor with patient. Photo Credit: iStock

Few genes are more important in human cancers than the infinitesimal molecule known as p53. It is known to provide robust protection from cancer, but when mutated, allows tumors to flourish.

Now, in a landmark study, Long Island scientists have found that p53 also plays a surprising -- and prominent -- role in strokes.

The finding is so important that the editors of the prestigious journal Cell, where the research was reported last week, put this major medical advance on its cover.

Researchers at the Stony Brook School of Medicine, led by Dr. Ute Moll, found that p53 -- sometimes called the guardian of the human genome -- sets off a cell-death signal that results in the irreversible destruction of brain tissue during a stroke.

For centuries doctors have known that brain tissue dies during a stroke. What no one knew until now is that the death signal not only rises from p53 but also combines with a protein to create a complex capable of extreme tissue damage. That is why strokes are so devastating, Moll said.

"This is a very important discovery," said Dr. Yusef Hannun, director of the Stony Brook Cancer Center. He noted that before Moll's discovery, he was most familiar with p53's role in tumor biology.

"P53 has been studied rather extensively since the mid-1980s," Hannun said. "But most [investigators] have focused on its role in cancer."

When the gene is healthy, he said, it acts as a molecular braking system, stopping the ill-fated series of events that lead to cancer.

Still, more than half of all forms of cancer possess p53 mutations. And in colon malignancies alone, up to 60 percent of patients carry damage in this critical gene, researchers have found.

Worse, mutations in p53 are also thought to underlie resistance to cancer drugs, one of the biggest problems facing cancer care today.

But in her research, Moll was able to open a new window of understanding.

It seems, according to Moll, that p53 genes are abundant between the two protective membranes that surround the cellular constituent known as the mitochondria.

These tiny bean-shaped powerhouses provide the energy for all human processes. The mitochondria produce the fuel required to walk up a flight of stairs, run around the block, or read the words on this page.

The moment a clot cuts off blood to a region of the brain -- the key event triggering a stroke -- is when p53 activates its death signal from deep inside the mitochondria.

"They are blowing up the cells," Moll said of p53 genes.

"The mitochondria are literally exploding," she added, having studied the process in lab mice. "Cells burst and lose their water. They become fragmented and spill out all their contents."

Moll also found that the drug cyclosporin A, long used to prevent tissue rejection after organ transplantation, can help save victims of stroke, if the medication is given within a window of a few hours. The drug blocks the p53-protein complex from furthering damage.

Moll's discovery of a cancer-associated gene playing a role in an unrelated condition is not an isolated medical advance.

Last year in another groundbreaking research project, Dr. Peter Davies and colleagues at the Feinstein Institute for Medical Research in Manhasset reported that a gene related to a form of leukemia also appears to have a hand in Alzheimer's disease.

That gene, known as c-ABL, has long been associated with chronic myeloid leukemia -- CML. But the Davies team found c-ABL abundant in the brain plaques and tangles of people with Alzheimer's.

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