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Protein necessary for the development and progression of all stages of pancreatic cancer
A study from the laboratory of Marina Pasca di Magliano, PhD was electronically published on January 9, 2012, in the prestigious Journal of Clinical Investigation. Dr. Pasca di Magliano is an Assistant Professor of Surgery at the University of Michigan, and received a Career Development Award from the Pancreatic Cancer Action Network in 2009, funded by Angus Mitchell in memory of Paul Mitchell. This grant was cited as one of the funding sources for this project.
Dr. Pasca di Magliano’s exciting research has focused on the protein K-Ras. K-Ras has been found to be mutated to an active form in over 90 percent of pancreatic cancer cases. Proteins such as K-Ras are considered oncogenes, which stimulate cancer by constantly signaling the cells to grow and survive. Healthy cells only grow and divide at the appropriate time and place, but tumor cells ignore normal cellular communications and grow in an unregulated manner.
Previously, a mouse model of pancreatic cancer has been developed whereby the mice are born with a mutated form of K-Ras specifically expressed in their pancreas. These mice develop pancreatic cancer in a stepwise manner, progressing from early cellular abnormalities to invasive cancer, mimicking human disease. Here, Dr. Pasca di Magliano and colleagues created a new mouse model with expression of K-Ras occurring in the pancreas in adult mice, rather than newborn. Further, the expression of mutant K-Ras can be turned on and off in this model. This allowed Dr. Pasca di Magliano and her colleagues to determine the effects of blocking the expression of mutant K-Ras at different time points throughout the progression of the disease.
The research team found that turning off mutant K-Ras expression during the early stages of precancerous disease caused the cells to revert back to normal, which is consistent with others’ observations that K-Ras mutation is a driving force for the initial development of pancreatic cancer. A less expected and quite striking finding was that removal of mutant K-Ras expression in mice with more advanced tumors was sufficient to induce cell death and cease the growth of the cancer cells. The fact that shutting down the expression of one protein was enough to kill the cancer cells suggests an “addiction” to the signaling generated by mutant K-Ras. Further research will be necessary to determine whether the expression or activity of mutant K-Ras can be therapeutically targeted.
Overall, these findings reinforce the significance of mutant K-Ras in the initation, development, and progression of pancreatic cancer.
Click here to read the scientific article.
Click here to learn more about Dr. Pasca di Magliano and other Pancreatic Cancer Action Network grant recipients.
