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Building a better mouse model to understand pancreatic cancer
Date:2/25/2014

ields from different institutions," says Mulvihill, who is also a pancreatic cancer surgeon and an investigator with the University of Utah's Huntsman Cancer Institute.

With a five-year survival rate of just 4.4 percent, cancer of the pancreas is the fourth leading cause of cancer deaths. In 82 percent of cases, the disease is found when it's too late to remove the tumor. Tumors that are smaller than 2 centimeters and haven't metastasized are considered the best cases for surgery. When tumors are operable, the five-year survival rate approaches 40 percent, according to Firpo.

IPMN is one of three classes of pancreatic cancer precursor lesions. Pancreatic Intraepithelial Neoplasia (PanIN) and mucinous cystic neoplasm (MCN) also are lesions that precede pancreatic cancer. PanINs are the lesions most commonly thought to lead to PDA.

Brg1 is an enzyme that regulates gene expression by altering DNA structure in the nucleus of a cell, a process known as chromatin remodeling. Hebrok found that when the Brg1 gene is knocked out in mice that are predisposed to PanIN development and subsequent PDA, lesions form that are similar to human IPMN. He confirmed that through the human IPMN samples from Mulvihill and Firpo.

But in addition to Brg1's role in forming IPMN lesions, Hebrok discovered that when the gene is knocked out in mice that have an activated gene called KRAS, whose role is to help regulate cell division, PanIN lesions occur less frequently. This indicates that Brg1 protects against PanIns but also helps cause IPMN lesions.

"As someone who researches pancreatic cancer, I think this discovery is significant because it defines mechanisms that lead to this cancer in ways that we didn't know about before," says Firpo, who's also a member of the Pancreas Cancer Research Program and Experimental Therapeutics Program at the University of Utah's Huntsman Cancer Institute. "It illuminates an area that were just guessing at b
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Contact: Phil Sahm
phil.sahm@hsc.utah.edu
801-581-2517
University of Utah Health Sciences
Source:Eurekalert

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