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[Cancer Research 63, 2016-2019, May 1, 2003]
© 2003 American Association for Cancer Research

Advances in Brief

Preinvasive Pancreatic Neoplasia of Ductal Phenotype Induced by Acinar Cell Targeting of Mutant Kras in Transgenic Mice1

Paul J. Grippo2, Patrick S. Nowlin, Michael J. Demeure3, Daniel S. Longnecker and Eric P. Sandgren4

Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706 [P. J. G., P. S. N., E. P. S.]; Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin 53226 [P. J. G., M. J. D.]; and Department of Pathology, Dartmouth Medical School, Hanover, New Hampshire 03755 [D. S. L.]

Activating mutation of the Kras oncogene is the most frequent and perhaps the earliest genetic alteration associated with pancreatic cancer. To examine the link between mutant Kras and exocrine pancreatic cancer, we generated transgenic mice carrying an elastase-mutant Kras transgene, which targets expression to pancreatic acinar cells. Most elastase-Kras founder mice displayed perinatal pancreatic acinar cell hyperplasia and dysplasia. However, adult mice in two surviving lineages displayed preinvasive pancreatic neoplastic lesions with ductal morphology, thereby providing a unique mouse model in which lesion histotype and initiating genetic alteration overlap with the human disease. Our findings suggest that Kras mutation is associated with development of early stage duct-like lesions in pancreas, but that additional alterations must accompany progression to malignancy.




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