A tumor-blocking protein previously implicated in prostate and breast cancer development may also be behind the most aggressive type of pancreas cancer. Scientists at the Kimmel Cancer Center at Jefferson in Philadelphia have discovered that the protein, pp32 - which normally applies the brakes on a cancer-causing gene - is missing in an aggressive form of pancreas cancer.

Though the work is preliminary, the researchers say, the absent protein could eventually become a marker for the disease and a potential drug target.

Researchers led by Jonathan Brody, Ph.D., assistant professor of Surgery, Charles Yeo, M.D., Samuel D. Gross Professor and chair of Surgery and Agnieszka Witkiewicz, M.D., assistant professor of Pathology, Anatomy and Cell Biology, all of Jefferson Medical College of Thomas Jefferson University, have shown in experimental models that without the protein, mutations in the cancer-causing gene K-ras can take over, turning cells malignant. Adding pp32 to pancreas cancer cells that have K-ras mutations and lack the protein can slow the growth of these fast-growing cells, leading the researchers to speculate that losing pp32 might be a critical event in determining how aggressively a pancreas cancer behaves. They report their initial findings online in the journal Modern Pathology.

As per Dr. Brody, prior laboratory and animal studies have shown that pp32 inhibits K-ras-activating gene mutations found in more than 90 percent of all pancreas cancers and in some early pre-malignant lesions as well. But in a subset of fast-moving, "poorly differentiated" pancreas cancers, the scientists observed that "pp32 is either reduced or lost," Dr. Brody says. "Losing the protein in pre-malignant lesions could be a marker for an aggressive form of pancreas cancer.

"It's rare to find laboratory studies that parallel what we see in actual pancreatic tumors," Dr. Brody says. "Connecting a protein that can inhibit a critical mutation found in almost every pancreas cancer to the pathology is powerful information. These types of studies can help us understand more about the early development of pancreas cancer on a molecular level.

"If we are able to learn more about this molecule, this may be a potential target that we could turn on in aggressive types of pancreas cancers," he notes. "In theory, if we could find a way to upregulate this molecule in these pancreas cancers, we may be able to arrest these fast-growing cancer cells as we did in experiments in this study. As we understand its molecular interactions, we could also somehow find the things that regulate it and extend our molecular understanding of this devastating disease."


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