Gene For Inherited Syndrome Is Possible New Tumor Suppressor

n as a tumor suppressor gene. Tumor suppressor genes work by producing a protein that helps prevent run- away cell division. If the gene is damaged and the protein doesn't work properly, uncontrolled cell proliferation -- and cancer -- can occur.

Initially, de la Chapelle and the other members of the research team had no idea what kind of protein the undamaged PJS gene produced, or what role that protein played in the cell.

But by comparing the structure of the PJS gene with already-known genes, they were startled to find that the PJS gene produces a type of enzyme known as a protein kinase.

"This surprised us," said de la Chapelle. "As far as we know, this is the first time a protein kinase gene has been identified as a tumor suppressor gene."

Cells have genes for many types of protein kinase enzymes, and some of these enzymes do play a role in causing cancer. But in those cases, cancer rises because the genes produce too much of the enzyme.

In PJS, on the other hand, cancer seems to occur because a protein kinase isn't produced.

"As of now," said de la Chapelle, "we have no clue as to how the loss of this gene might lead to cancer. That work will require many experiments to learn what other proteins this protein interacts with and how this particular gene might fit into one of the cancer-producing pathways."

"The intriguing thing here is that this unusual disorder is characterized by the occurrence of polyps in the intestine that are often premalignant, and by the presence of peculiar freckle-like spots on the lips and the skin around the mouth and on the fingers. How these two relate to each other is absolutely unknown."

Furthermore, he said, "the combination of tumors that can occur with this syndrome really gives no clue to what's going on. That is truly intriguing."

The work on PJS continues in de la Chapelle's laboratory with studies he hopes will reveal how mutations in the PJS gene predispose an individual to cancer.


Contact: Albert de la Chapelle
(614) 688-4781
Ohio State University

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