Newly identified tumour suppressor provides therapeutic target for prostate cancer
03 Apr 2013
Scientists at Sanford-Burnham Medical Research Institute (Sanford-Burnham) have identified how an enzyme called PKC? suppresses prostate tumour formation. The finding, which also describes a molecular chain of events that controls cell growth and metastasis, could lead to novel ways to control disease progression.
Working in close collaboration, the labs of Maria T. Diaz-Meco, Ph.D., and Jorge Moscat, Ph.D., found that PKC? controls the activation of a pro-tumour gene called c-Myc. Normally, PKC?'s alteration keeps c-Myc in check. But PKC? levels are low in prostate and other cancers, leaving c-Myc free to enhance cell growth and metastasis. This study, published April 1 in the Proceedings of the National Academy of Sciences, suggests that restoring PKC? could provide a new approach to treating prostate cancer.
How PKC? acts as a prostate tumour suppressor
Previous studies suggested that PKC? might act as a tumour suppressor-but that wasn't clear in the case of prostate cancer. In their study, the team learned of PKC?'s role after genetically engineering mice so they lacked the enzyme altogether.
"In this study, we assessed the role of PKC? in prostate cancer, and for the first time we used a knockout mouse for PKC? to demonstrate that it's actually a tumour suppressor," Diaz-Meco said. "But, I think the major advance in this paper is that we found out how PKC? is a tumour suppressor in prostate cancer."
In their study, the researchers found that PKC? suppresses tumors in cooperation with a gene called PTEN. PTEN has been long known to act as a tumour suppressor, and it's also well-established that its mutated form is common in prostate cancer.
But the loss of normal PTEN function alone doesn't lead to aggressive prostate cancer. According to this study, the loss of PKC? and the resulting over-active c-Myc are also needed for aggressive prostate cancer to develop.
Potential approaches toward attacking prostate cancer may in the future involve activating PKC? through gene therapy, or dealing with its inaction downstream-perhaps by finding another way to inhibit c-Myc in the absence of PKC?.
