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Study reveals first genetic step necessary for prostate cancer growth

one copy of the Rb gene in prostate cells, mice developed a condition known as focal hyperplasia, characterized by precancerous growths. Nearly a year after they formed, the growths did not become cancerous.

"This suggests to us that loss of a single copy of Rb can initiate this excess cell growth but is not sufficient for cancer to develop," Greenberg said. "Perhaps the most significant finding was that loss of the second copy of Rb an event previously thought to be essential for tumor progression did not appear to accelerate the disease. Losing one copy was enough to get things going."

While Greenberg had previously demonstrated that combined loss of Rb and related proteins and the p53 tumor suppressor would predispose mice to develop aggressive prostate cancer, the role of Rb in tumor initiation remained enigmatic. Further research is needed to determine which secondary mutations can push these early stage growths into prostate cancer. Greenberg said that tests to distinguish between men who only have Rb mutations and those who have acquired additional genetic defects could help doctors decide when or whether aggressive treatment is warranted.

"Right now, there is no way to absolutely predict at an early stage whether a man's prostate cancer is slow-growing and non-lethal, meaning that many men receive unnecessary treatment that can cause serious side effects," he said.

Scientists have had a difficult time establishing the causal relationship between genes and cancer, Greenberg said. "We've addressed this by using a mouse system that allows us to selectively eliminate genes in the epithelial cells of the prostate. Our experimental approach allows us to closely mimic what happens in man and gives us a glimpse into the natural history of the disease that we haven't had before." Greenberg developed a widely used genetically engineered strain of mice that develops prostate cancer at the Baylor College of Medicine prior to joining Fred Hutc
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Contact: Dean Forbes
dforbes@fhcrc.org
206-667-2896
Fred Hutchinson Cancer Research Center
1-Sep-2004


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