The study, published in the Sept. 1 issue of Cancer Research, found that when mice are engineered to lose a single copy of a gene called Rb in their prostate, they develop a precancerous condition analogous to the earliest stages of human prostate cancer. Importantly, in the absence of additional genetic defects, the mice do not develop full-blown prostate cancer.
This suggests that the loss of Rb in prostate cells could be the initial spark that in some men eventually leads to prostate cancer, said senior author Norman Greenberg, Ph.D., a member of Fred Hutchinson's Clinical Research Division.
"Finding the loss of Rb is like seeing smoke," he said. "We now need to figure out the genetic predictors for fire."
To identify genetic events that cause early-stage prostate cancer, Greenberg and colleagues focused on the Rb gene. The gene is known to be defective in a variety of cancer types, including up to 60 percent of human prostate cancers. Rb is a member of a family of genes known as tumor suppressors, which normally work to keep cells dividing at a healthy pace. Cells with defective or missing tumor suppressors lose their brakes on cell division, a hallmark of cancer.
The researchers developed a system using mice that were genetically engineered to self-destruct one or both copies of its Rb gene in prostate cells. The important difference between these mice and the standard gene knock-out strategy is that the Rb gene stays intact in all other tissues of the animal, a situation that closely resembles how genes are inactivated or lost in cancers that occur sporadically in humans.