Researchers at the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), have found that inhibition of the same protein produces different effects in mouse cell lines depending on whether those cell lines expressing normal or cancerous forms of Kit, a cell surface receptor. These findings, appearing in the journal Blood online on November 12, reveal a potential new target for treating certain blood cell disorders.
Kit is critical for the development of certain blood cells, and mutations in Kit are associated with several diseases in mast cells, a type of white blood cell involved in immune responses. Gleevec, a drug that inhibits Kit and other related proteins, has been useful in the treatment of diseases associated with these proteins, including gastrointestinal stromal cell tumors and chronic myeloid leukemia. However, an activating mutation in Kit commonly found in mast cell disease and some forms of acute myeloid leukemia is resistant to Gleevec. Therefore, one potential method of circumventing a drug-resistant form of Kit would be to target one or more of the proteins activated by it.
NCI researchers Diana Linnekin, Ph.D., and Tanya Jelacic, Ph.D., found that inhibition of one such Kit activated protein, PKCδ <PKCdelta> (a member of a family of protein kinases involved in cell signaling), reduced the growth of a mouse mast cell line expressing mutant Kit by approximately 40 percent, while the growth of normal mast cells was not inhibited. "This is the first demonstration of a function change in PKCδ <PKCdelta> resulting from an oncogenic mutation in a growth factor receptor," said Linnekin.
These results suggest that PKCδ <PKCdelta> may be a therapeutic target for diseases associated with mutations in Kit, since anti-PKCδ <PKCdelta> drugs would specifically inhibit the growth of mutated cells and not affect normal ones. "This work is a promising study on cancer inhibition," said Linnekin. "Dr. Jelacic and I believe that follow-up work with human cell lines, as well as work in mouse models of cancer, would be definitely worthwhile."
For more information about cancer, visit the NCI Web site at http://www.cancer.gov or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
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