042-AP-00
EMBARGOED UNTIL 3 P.M. PST, TUESDAY, APRIL 4, 2000
KEY PROTEIN IN GENETIC PATHWAY LEADING TO COLON CANCER FOUND FOR FIRST TIME IN CANCER CELLS BY UC IRVINE RESEARCHERS
Study 0n Fruit Flies and Humans May Help Determine Link Between Gene Mutations, Rates of Colon Cancer
Irvine, Calif. - A team led by a UC Irvine College of Medicine researcher has found for the first time a protein in cancerous cells that may be linked to colon cancer. The findings provide a more detailed picture of how disruptions of certain genes and proteins could lead to colon cancer and may help researchers find new ways to prevent and treat the disease.
Dr. Randall Holcombe, associate director of the Chao Family Comprehensive Cancer Center at UCI, led a team of researchers that found a protein called LEF1 in colon cancer cells. LEF1 is part of a group of proteins and genes that form a pathway in cells that controls cellular growth in the body. The study will be presented Tuesday, April 4, at the American Association of Cancer Research annual meeting in San Francisco.
"These findings, which started with research on fruit flies, bring us one step closer to understanding why colon cancer can begin spontaneously in people without family histories of the disease," Holcombe said. "About 85 percent of these spontaneous colon cancers show mutations in the genetic pathway we're studying; a better understanding of how this pathway works can help scientists develop better diagnostic tools to detect colon cancer early and to target people who may be at risk."
Mutations of genes in this pathway cause excess production of proteins called beta-catenin, which binds to a group of other proteins in cells called LEF/TCF. Once bound together, this complex of beta-catenin and LEF/TCF proteins attaches to strands of DNA, activating other genes that promote growth. Overproduction of this complex of proteins activates rampant cell growth, leading to cancer.
While TCF is found in both normal and cancerous cells in the colons of humans and animals, the researchers for the first time found LEF1 in colon cancer cells taken from six patients. However, LEF1 was not found in either normal cells or in pre-cancerous polyps in the colon.
"Something is activating LEF1 in cancer but isn't activating it in the normal colon or in the polyp stage of growth," Holcombe said. "If we know what is switching on LEF1, we may be able to understand which mutations are more likely to lead from pre-cancerous polyps to colon cancer and find ways to either prevent those mutations from taking place or treat the results of those mutated genes. Since these molecules exist in so many cells, they may be useful in understanding melanoma and other cancers, as well."
Colon cancer is one of the nation's most common cancers, affecting more than 120,000 men and women every year. The disease kills about 56,000 annually, making it the second deadliest cancer in the country, according to the American Cancer Society. In most cases, its cause is unknown.
The UCI researchers are now looking at other genes and proteins that seem to work alongside this fl-catenin/LEF1/TCF pathway, which may yield more insight on how specific genes and proteins interact to cause cancer.
Holcombe's colleagues in the study were J. Lawrence Marsh, chair of the Department of Developmental and Cell Biology; Marian L. Waterman, assistant professor of microbiology and molecular genetics; research assistant Tatjana Milovanovic, and laboratory technologist Trung Truong.
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Contact:Andrew Porterfield
(949) 824-3969
[email protected]
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