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Release: August 22, 2000

UI researchers get $800,000 from NIH to investigate processes that make cells cancerous

IOWA CITY, Iowa -- University of Iowa researchers have been awarded a five-year, $800,000 grant from the National Institutes of Health to study how human epithelial cells become immortal. Immortalization of cells is a key event in the development of cancer.

The research team, led by Aloysius J. Klingelhutz, Ph.D., UI assistant professor of microbiology, will investigate the mechanisms that allow these cells to avoid a natural death. Klingelhutz believes that two processes are involved: activation of an enzyme that repairs the fraying ends of chromosomes and inactivation of a cellular pathway called the retinoblastoma (Rb) pathway, which is involved in determining whether a cell should replicate its DNA and divide.

As normal cells divide, the DNA at the chromosome ends gets progressively shorter until a point is reached where the cells die. This type of cell-death is a normal process. However, an enzyme called telomerase is capable of rebuilding the frayed chromosome ends. Telomerase, which is not usually active in most cells, is very active in cancer cells. This has led to speculation that the telomerase activity makes cells immortal. However, according to Klingelhutz, this activation on its own is not enough to make the cells immortal because the Rb pathway also has to be overcome.

"By using unique epithelial cell model systems developed in our laboratory, we will identify factors involved in controlling the Rb pathway during the normal cell-death process," said Klingelhutz. "This work is likely to significantly increase our understanding of the early stages of carcinogenesis."

The team will also seek to determine how telomerase is activated as cells become immortal. "We hope that this research will eventually lead to new and innovative strategies for the prevention, diagnosis and treatment of human cancer," Klingelhutz said.


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