The gene, PUMA, or p53 up-regulated modulator of apoptosis, is controlled by p53 - a tumor-suppressing gene that prevents normal cells from turning into life-threatening tumor cells. Previous research has determined that damage to p53 is fundamental to the development of a vast majority of cancers, and inactivation of the growth-controlling function of p53 is critical to the growth and spread of most cancers.
The leading investigators of the study, Lin Zhang, Ph.D., assistant professor of pharmacology, University of Pittsburgh and Jian Yu, Ph.D., assistant professor of pathology, University of Pittsburgh, performed several gene targeting experiments involving PUMA and found that if the gene is deleted in colorectal cancer cells, cell death is prevented. These findings build on previous findings published in 2001 in Molecular Cell, where the same research team identified PUMA as a novel gene that when expressed, resulted in rapid and profound apoptosis.
"This research results from our interest in looking at how cancer cells die when treated with anti-cancer therapies and why chemotherapy often fails to destroy cancer," said Dr. Yu. "We have learned that when we get rid of PUMA in cancer cells, the cells are more resistant to dying compared to their counterparts that have intact PUMA."
"Given these findings, our next step is to look for compounds that elevate the level of PUMA in colorectal cancer cells, enabling us to test promising new therapies for cancer. PUMA itself is also an attractive target for gene therapy. At UPCI, we are trying to expand these approaches to a variety of cancers," said Dr. Zhang.
This study was funded, in part, by a grant from the National Institutes of Health. Co-authors of the study include, Zhenghe Wang, Ph.D., Kenneth W. Kinzler, Ph.D., and Bert Vogelstein, M.D., all with the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University.
World-renowned for innovative approaches to cancer prevention, detection and diagnosis, UPCI recently relocated to the Hillman Cancer Center at UPMC Shadyside Hospital. The Hillman Cancer Center is the flagship facility for both UPCI and the UPMC Cancer Centers - a network of more than 30 office-based medical oncology practices and regional cancer centers that provide the highest standard of care for patients throughout western Pennsylvania. UPCI and the UPMC Cancer Centers' program in cancer currently ranks 11th in the country.
For more information on this and other ongoing research projects at UPCI, please visit www.upci.upmc.edu.