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University of Iowa News Release

Dec. 18, 2003

Photo: Frederick Domann, Ph.D., associate professor of radiation oncology in the Free Radical and Radiation Biology Graduate Program

UI Researchers Receive Grant To Study Control Of Tumor Suppressor Gene

Researchers in the Roy J. and Lucille A. Carver College of Medicine at the University of Iowa have been awarded a five-year, $1.3 million grant renewal from the National Cancer Institute (NCI) to study factors controlling the expression of a tumor suppressor gene. The long-term goal of the UI study is to understand the mechanisms that control expression of this important gene and to use that information to determine molecular targets that might lead to novel cancer therapies.

Tumor suppressor genes, as the name suggests, prevent cells from becoming cancerous. If tumor suppressor genes are impaired or switched off, cancerous changes can take hold of a cell and cancer can develop. The UI study, led by Frederick Domann, Ph.D., associate professor of radiation oncology in the Free Radical and Radiation Biology Graduate Program, will focus on the SOD2 gene, an important antioxidant enzyme and tumor suppressor gene.

In many types of cancer, levels of the superoxide dismutase (SOD) antioxidant protein are low compared to levels in normal cells. This suggests that the SOD2 gene might function as a tumor suppressor gene. Domann and his colleagues are interested in understanding what happens at the genetic level to cause low levels of SOD. The researchers hope this information will suggest ways to reactivate the SOD2 gene -- a process that might lead to new cancer therapies.

"Reactivating SOD2 expression in human cancer cells will have the effect of slowing down their growth and spread, thus decelerating the rate of cancer progression," Domann said.

Previous research from Domann's lab suggests that SOD2 gene expression is regulated in part by so-called epigenetic factors. Unlike direct genetic mutations, which alter a gene's sequence, the epigenetic changes that Domann and his colleagues will study alter how a gene gets switched on or off.

The research team seeks to better understand how epigenetic changes affect SOD levels. An understanding of these mechanisms might lead to the development of drugs to block the epigenetic processes that turn off tumor suppressor genes like SOD2.

"Development of pharmacological strategies to reactivate aberrantly silenced tumor suppressor genes to impact human cancer therapy is a major focus of research in our laboratory," Domann said. "Findings obtained through this research will have wide-reaching implications for understanding and controlling epigenetic regulation of many other tumor suppressor genes important to cancer progression."

University of Iowa Health Care describes the partnership between the UI Roy J. and Lucille A. Carver College of Medicine and UI Hospitals and Clinics and the patient care, medical education and research programs and services they provide. Visit UI Health Care online at www.uihealthcare.com.

STORY SOURCE: University of Iowa Health Science Relations, 5141 Westlawn, Iowa City, Iowa 52242-1178

CONTACT: Jennifer Brown, (319) 335-9917 jennifer-l-brown@uiowa.edu

PHOTOS/GRAPHICS: A photos of Dr. Domann is available at http://www.uihealthcare.com/depts/med/radiationoncology/frrb/faculty/domann.html