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August 3, 2002 |
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Gene associated with Huntington's disease linked to cancer By Sally Pobojewski ANN ARBOR, Mich. -- Aug. 4, 2002 -- A protein with an intriguing connection to the gene for Huntington's disease could help physicians diagnose and more effectively treat patients with two of the most common and deadly forms of cancer, according to a new study. Absent in normal prostate and colon epithelial cells, but found in large amounts in prostate, colon and other tumor cells, it is called "huntingtin" interacting protein or HIP1. The protein has never before been associated with any type of cancer according to the University of Michigan research team led by Dr. Theodora Ross. (Editor's: Note huntingtin is the correct spelling.) "Anytime you find a true marker for cancer, it's surprising," Ross, an oncologist in the U-M's Comprehensive Cancer Center said in a prepared statement. "But HIP1 also is unusual, because it seems to be such a strong prognosticator, especially for prostate cancer." Results of U-M research on HIP1's relationship to human prostate and colon cancer were published August 1 in the Journal of Clinical Investigation. Huntington's is an inherited degenerative disease of the brain that causes people in the prime of life to begin losing muscle control. It becomes progressively worse over time and is eventually fatal. In her study, Ross first measured levels of HIP1 expression in 60 cancer cell lines and a tissue microarray of primary tumors from the National Cancer Institute, which included hundreds of tissue samples from colon, breast, melanoma, ovarian, prostate, kidney and lung cancer. To quantify HIP1 expression in different stages of prostate cancer, U-M researchers used tissue samples from the U-M Prostate Specialized Program of Research Excellence (SPORE) tumor bank, funded by the National Cancer Institute. What Ross' team found in all cancer types and in prostate cancer in particular surprised them. "We don't find significant HIP1 expression in normal prostate epithelial cells, but as prostate cancer develops and progresses, we see a steady increase in HIP1 expression," said Ross, an assistant professor of internal medicine in the U-M Medical School. "HIP1 was expressed in 50 percent of tumors from patients in the earliest stages of cancer, 88 percent of tumors from patients with localized prostate cancer, and 100 percent of patients with metastatic prostate cancer. "High levels of HIP1 were present in every stage of colon cancer. In melanoma, breast and ovarian cancers, the expression patterns varied, but HIP1 was consistently over-expressed," Ross said. During her post-doctoral fellowship at Boston's Dana-Farber Cancer Institute, Ross cloned the protein from bone marrow cells of a patient with leukemia. Since joining the U-M Medical School three years ago, she has focused her research on HIP1 and its relationship to an important cellular trafficking and signaling system called the clathrin-mediated trafficking pathway. Cells use this system to remove old receptors and signaling molecules on cell surfaces and replace them with new molecules. The HIP1 protein appears to be involved in this process, according to Ross, along with another protein called htt, which is expressed by the mutated gene responsible for Huntington's disease. Although both proteins are found in parts of the cell where movement of material occurs, their exact role is unknown. "This is a new pathway in tumorigenesis; no one else is working with it in this context," Ross said. "Our paper is the first demonstration of a connection between tumor formation and a protein involved in this cell trafficking pathway." Ross' laboratory is now trying to understand the relationship between HIP1 and cancer cells. If scientists can discover the functional relationship between HIP1 and cancer, Ross believes it should be possible to develop agents that could kill prostate and colon tumor cells without harming the normal epithelial cells lining the inside of these organs. The research study was funded by the Huntington's Disease Society of America, the National Institute of General Medical Sciences and the Cancer Research Fund of the Damon Runyon Foundation. SOURCE: Journal of Clinical Investigation 110:3, 351-360, 2002 |
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