Key Discovery: Scientists Find Inactive Gene Promotes Cancer

February 13, 1997

CHAPEL HILL -- Two years ago, scientists at the University of North Carolina at Chapel Hill and colleagues demonstrated for the first time that when a tumor-killing gene called p53 becomes inactive, tumors spread aggressively. That work, done in mice and considered important medical research news, confirmed p53's key role in protecting mammals -- probably including humans -- from cancer.

Now the scientists have taken their work a step further. They have discovered that another gene known as "bax" also is involved in killing cancerous cells. When the bax gene fails to work in harmony with p53, fewer malignant cells are killed, and tumors grow faster, the new research shows.

A report on the findings appears in the Feb. 13 issue of the journal Nature. Authors are Drs. Chaoying Yin and Terry Van Dyke, postdoctoral fellow and associate professor, respectively, in biochemistry and biophysics at the UNC-CH School of Medicine and Drs. C. Michael Knudson and Stanley J. Korsmeyer, both of molecular oncology at Washington University in St. Louis.

"The tumor suppressing p53 gene is mutated in about 50 percent of human cancers, which means that its protective function is lost," said Van Dyke, a member of the UNC Lineberger Comprehensive Cancer Center. "That"s a large number, but still only half. It is likely that in the other half of cancer cases, mutations occur elsewhere in the series of defensive responses that come about when a tumor starts growing."

To test the idea that bax somehow contributes to p53's effectiveness, Yin and Van Dyke used both mice developed at Washington University that lacked the bax gene and a tumor model developed at UNC-CH in Van Dyke's laboratory. They found that cancer cell death dropped by 50 percent in the bax-deficient mice compared to mice whose bax gene operated properly.

"To our knowledge, this is the first demonstration that bax acts as a tumor suppresser as we and others have suspected," Van Dyke said.

If the finding holds up in humans as expected, the gene could become a target for gene therapy or other cancer therapies, she said. The more targets available for treatment, the more effective treatment is likely to be. Also, just knowing if the gene has mutated and no longer helps kill cancerous cells could aid doctors by showing which patients need the strongest treatment.

"One of the aspects of cancer that we know least about is the process that causes tumors, which are not life-threatening in their early stages, to change and become aggressive, which is life-threatening," the researcher said. "We think this work is another important piece of the puzzle."

Van Dyke's scientific work has become increasingly personal for her, she said. Recently her mother was diagnosed with lung cancer.

"My mother's illness has had a big impact on me," she said. "It has made me look more at the human side of this illness."

Note: Van Dyke can be reached Thursday and Friday until noon at the Georgetown Inn Hotel (202) 333-8900. After about 2 p.m. Friday, she can be reached at (919) 962-2145 or 2148 (w) or 933-7210 (h).

Contact: David Williamson

University of North Carolina at Chapel Hill

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