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Newly identified tumor suppressor provides therapeutic target for prostate cancer

Date:
April 1, 2013
Source:
Sanford-Burnham Medical Research Institute
Summary:
Researchers have found that the enzyme PKCzeta controls the activation of a pro-tumor gene called c-Myc. Normally, PKCzeta's alteration keeps c-Myc in check. But PKCzeta levels are low in prostate and other cancers, leaving c-Myc free to enhance cell growth and metastasis.
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Prostate cancer cells expressing a mutant form of c-Myc that cannot be altered by PKCzeta (left) are more aggressive and more invasive than prostate cancer cells in which PKCzeta is able to keep tabs on c-Myc (right).
Credit: Sanford-Burnham Medical Research Institute

Researchers have identified how an enzyme called PKCζ (PKCzeta) suppresses prostate tumor 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 PKCζ controls the activation of a pro-tumor gene called c-Myc. Normally, PKCζ's alteration keeps c-Myc in check. But PKCζ levels are low in prostate and other cancers, leaving c-Myc free to enhance cell growth and metastasis. This study, appearing online April 2 in the Proceedings of the National Academy of Sciences, suggests that restoring PKCζ could provide a new approach to treating prostate cancer.

How PKCζ acts as a prostate tumor suppressor

Previous studies suggested that PKCζ might act as a tumor suppressor -- but that wasn't clear in the case of prostate cancer. In their study, the team learned of PKCζ's role after genetically engineering mice so they lacked the enzyme altogether.

"In this study, we assessed the role of PKCζ in prostate cancer, and for the first time we used a knockout mouse for PKCζ to demonstrate that it's actually a tumor suppressor," Diaz-Meco said. "But, I think the major advance in this paper is that we found out how PKCζ is a tumor suppressor in prostate cancer."

In their study, the researchers found that PKCζ suppresses tumors in cooperation with a gene called PTEN. PTEN has been long known to act as a tumor 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 PKCζ 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 PKCζ through gene therapy, or dealing with its inaction downstream -- perhaps by finding another way to inhibit c-Myc in the absence of PKCζ.

This research was funded by the U.S. National Institutes of Health (National Cancer Institute grants R01CA134530, R01CA132847, and 5P30CA030199-31; National Institute of Allergy and Infectious Diseases grant R01AI072581; National Institute of Diabetes and Digestive and Kidney Diseases grant R01DK088107) and the Department of Defense (grant DoD-PC080441).


Story Source:

The above post is reprinted from materials provided by Sanford-Burnham Medical Research Institute. The original item was written by Bruce Lieberman. Note: Materials may be edited for content and length.


Journal Reference:

  1. Ji Young Kim, Tania Valencia, Shadi Abu-Baker, Juan Linares, Sang Jun Lee, Tomoko Yajima, Jing Chen, Alexey Eroshkin, Elias A. Castilla, Laurence M. Brill, Mario Medvedovic, Michael Leitges, Jorge Moscat, and Maria T. Diaz-Meco. c-Myc phosphorylation by PKCζ represses prostate tumorigenesis. Proceedings of the National Academy of Sciences, 2013; DOI: 10.1073/pnas.1221799110

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Sanford-Burnham Medical Research Institute. "Newly identified tumor suppressor provides therapeutic target for prostate cancer." ScienceDaily. ScienceDaily, 1 April 2013. <www.sciencedaily.com/releases/2013/04/130401181504.htm>.
Sanford-Burnham Medical Research Institute. (2013, April 1). Newly identified tumor suppressor provides therapeutic target for prostate cancer. ScienceDaily. Retrieved July 2, 2015 from www.sciencedaily.com/releases/2013/04/130401181504.htm
Sanford-Burnham Medical Research Institute. "Newly identified tumor suppressor provides therapeutic target for prostate cancer." ScienceDaily. www.sciencedaily.com/releases/2013/04/130401181504.htm (accessed July 2, 2015).

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