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Pancreatic cancer study reveals mechanism initiating disease, in mice
Date:3/12/2010

UCSF scientists have discovered how a mutated gene known as Kras is able to hijack mouse cells damaged by acute pancreatitis, putting them on the path to becoming pancreatic cancer cells.

The finding, they say, suggests one way in which the mutated gene -- found in nearly all cases of the most common and lethal form of pancreatic cancer -- exacts its toll in humans. It also strengthens evidence that chronic pancreatitis, which occurs when digestive enzymes become activated too soon, causing abdominal pain, indigestion and other symptoms, may be a risk factor in the development of pancreatic cancer, rather than a side effect.

The finding, says senior author Matthias Hebrok, PhD, the Hurlbut-Johnson Distinguished Professor in Diabetes Research and interim director of the UCSF Diabetes Center, could help scientists in their search for diagnostic markers in the blood of pancreatic cancer, as well as targets for therapy.

While evidence from patient tissue and mouse studies has indicated that pancreatic ductal adenocarcinoma (PDA) evolves from cells known as ductal cells -- which line the ducts through which digestive enzymes are transported from the pancreas to the small intestine -- recent studies by other labs have shown that PDA can emerge from so-called acinar cells, which produce digestive enzymes.

Subsequently, scientists in other labs have confirmed that mutated Kras can initiate the development of precursors to PDA in acinar cells. However, the findings have been puzzling, because expression of mutated Kras does not guarantee acinar reprogramming.

Given this inconsistency, scientists have hypothesized that other events in the cellular environment must occur for mutated Kras to assert itself, and recent studies have indicated that acute and chronic pancreatitis may be one such factor. When mutant Kras is active in the acinar cells of mice with chemically-induced acute pancreatitis, the development of precursors
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Contact: Jennifer OBrien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
Source:Eurekalert

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