Cellular Pathway Identified That Makes Prostate Cancer Fatal

“A number of cancer researchers are interested in microRNAs and how they are involved in diseases like leukemia,” said Ralph deVere White, director of the UC Davis Cancer Center, professor of urology and senior author on the study. “But this is the first research to specifically look at the functional effects of microRNAs on the progression of prostate cancer.”

Relatively new discoveries in genetic research, microRNAs are small, single strands of RNA that regulate gene expression processes between larger strands of RNA. Working with 19 samples from the cancer center’s repository of prostate cancer cells, deVere White and his team used high-resolution analysis techniques to identify microRNAs that were differentially expressed. Of five that were distinct, one – miR-125b – caught their attention because of its presence at high levels in both androgen-dependent and androgen-independent prostate cancer cells.

Androgens, such as testosterone, are known to promote tumor growth. While androgen suppression treatments slow the progress of prostate cancer, they do not cure it.

“One of the most confounding things about prostate cancer is that after a period of success with androgen suppression therapy, the cancer starts to thrive again,” deVere White explained. “That’s when the disease becomes fatal. This particular microRNA supports the ability of prostate cancer cells to exist and grow in its androgen-independent state. And we currently have no effective treatments for the androgen-independent state of the disease.”

Now having identified a cellular link between the two phases of prostate cancer, deVere White and colleagues are hopeful that miR-125b screening will at some point become a standard diagnostic tool and that genetic and chemotherapy treatments can be developed that remove this essential survival mechanism for cancer cells. Before this can happen, the team needs to first find out if a microRNA “knockout” can be safely accomplished.

“We simply don’t know yet all that microRNAs do for us,” said deVere White. “We will use animal models to see if we can reduce or remove one of more of them without interfering with other essential molecular functions.”

Another important next step is to identify the full range of microRNAs involved in prostate cancer.

“There are believed to be thousands of microRNAs, and we have only identified a handful that is important to prostate cancer,” said Xu-Bao Shi, a project scientist with the UC Davis Department of Urology and lead author on the study. “We must next identify if others are involved along with their regulating patterns and mechanisms in order to gain a more comprehensive picture of how they contribute to the onset and progression of the disease. Our study definitely opens up a whole new avenue in prostate cancer research.”

Besides skin cancer, prostate cancer is the most common malignancy in American men. It is estimated that 218,890 men in the United States will be diagnosed with and 27,000 men will die of prostate cancer in 2007.

The study will be published in the Proceedings of the National Academy of Sciences.