There are so many things that go wrong in prostate cancer, and some of them are tiny. MicroRNAs fall into this category. They're little factory workers — molecules that help regulate cells' production of specific proteins. Their job is small but important; what they do or don't do can affect cell growth, death, and differentiation (how "normallooking" the cell is; healthy cells are well differentiated; cancer cells are poorly differentiated). Alterations in the work of these microRNAs have been found in several different cancers, including prostate cancer. "Both increased and decreased expression of certain microRNAs are known to affect cancer cells," explains Brady scientist William G. Nelson, M.D, Ph.D. Although nobody knows for sure which particular switch turns microRNAs up or down, Nelson suspects that methylation of certain sections of DNA called cytosine bases may play a big role here. "This type of change has been found to affect many types of genes in prostate cancer," Nelson says. In studies of human prostate cancer cells, Nelson is looking for these changes near 37 microRNA genes, using a new technique developed in his laboratory, called COMPARE-MS.

“We hope our findings can
lead to new diagnostic tests,
and to new strategies for
treating and even for preventing
prostate cancer.”

The next step, Nelson says, is to try to reverse the abnormal cytosine methylation patterns, "and see whether we can restore the normal expression of the microRNAs. We hope our findings can lead to new diagnostic tests, and to new strategies for treating and even for preventing prostate cancer."

In another series of studies, Shawn Lupold, Ph.D., the Virginia and Warren Schwerin Scholar, is investigating how hormones affect microRNAs — and how this, in turn, affects prostate cancer. Specifically, he wants to find out how male hormones, called androgens, and vitamin D — known to be very important in regulating normal and cancerous prostate cells — affect microRNAs in the prostate. He believes that these microRNAs, in turn, significantly affect prostate cell growth, differentiation, and death. "These studies should reveal abnormal microRNAs that exist within prostate cancer, and what we learn may be very important in developing new forms of treatment."