Protein prevents tissue injury but encourages tumor growth

Aug. 11, 2005 -- You win some, you lose some. A protein that protects the body from tissue damage also increases the risk of tumors, according to a study conducted at Washington University School of Medicine in St. Louis. Moderate reduction of the protein level protects against tumor formation but increases susceptibility to tissue injury.

Because of its protective function in the body, the protein potentially could be used to selectively shield cells from toxic therapies, according to senior author Steven J. Weintraub, M.D., an investigator with the Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital.

The protein, called Bcl-xL, has the ability to help keep cells alive, but does so by interfering with programmed cell death, or apoptosis, a process that can rid the body of unwanted or damaged cells.

"We earlier found that Bcl-xL helps the body's healthy cells survive the effects of toxic chemotherapeutic agents," says Weintraub, assistant professor of surgery and of cell biology and physiology. "This new study clearly demonstrates a trade-off by showing that normal levels of Bcl-xL encourage the growth of tumors in mice exposed to a carcinogen."

The study, appearing in Oncogene's advance online publication, compared the effect of urethane, a lung-specific carcinogen, on two sets of mice: wild-type mice, which have two functional genes that express Bcl-xL, and transgenic mice that have only one functional gene expressing Bcl-xL. Because they have only one of the genes, the transgenic mice produce less Bcl-xL.

After exposure to urethane, 40 percent of wild-type mice developed seven or more lung tumors, while no transgenic mice developed more than seven tumors. Furthermore, wild-type mice on average had larger tumors than transgenic mice.

"In light of the detrimental effect of normal Bcl-xL levels in terms of tumor growth, we wanted to carefully assess the protein's beneficial effect--its

Contact: Gwen Ericson
Washington University School of Medicine

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