10. Gidekel Friedlander SY, Chu GC, Snyder EL, Girnius N, Dibelius G, et al. (2009) Context-dependent transformation of adult pancreatic cells by oncogenic K-Ras. Cancer Cell 16: 379–389. 11. Blaine SA, Ray KC, Anunobi R, Gannon MA, Washington MK, et al. (2010) Adult pancreatic acinar cells give rise to ducts but not endocrine cells in response to growth factor signaling. Development 137: 2289–2296. 12. Ray KC, Bell KM, Yan J, Gu G, Chung CH, et al. (2011) Epithelial tissues have varying degrees of susceptibility to Kras(G12D)-initiated tumorigenesis in a mouse model. PLoS ONE 6: e16786. 13. Lowenfels AB, Maisonneuve P (2006) Epidemiology and risk factors for pancreatic cancer. Best Pract Res Clin Gastroenterol 20: 197–209. 14. Carriere C, Young AL, Gunn JR, Longnecker DS, Korc M (2009) Acute pancreatitis markedly accelerates pancreatic cancer progression in mice expressing oncogenic Kras. Biochem Biophys Res Commun 382: 561–565. 15. Morris JPt, Cano DA, Sekine S, Wang SC, Hebrok M (2010) Beta-catenin blocks Kras-dependent reprogramming of acini into pancreatic cancer precursor lesions in mice. J Clin Invest 120: 508–520. 16. Fukuda A, Wang SC, Morris JPt, Folias AE, Liou A, et al. (2011) Stat3 and MMP7 contribute to pancreatic ductal adenocarcinoma initiation and progression. Cancer Cell 19: 441–455. 17. Tronche F, Kellendonk C, Kretz O, Gass P, Anlag K, et al. (1999) Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety. Nat Genet 23: 99–103. 18. Soriano P (1999) Generalized lacZ expression with the ROSA26 Cre reporter strain. Nat Genet 21: 70–71. 19. Willemer S, Elsasser HP, Adler G (1992) Hormone-induced pancreatitis. Eur Surg Res 24 Suppl 1: 29–39. 20. Neuschwander-Tetri BA, Burton FR, Presti ME, Britton RS, Janney CG, et al. (2000) Repetitive self-limited acute pancreatitis induces pancreatic fibrogenesis in the mouse. Dig Dis Sci 45: 665–674. 21. Jensen JN, Cameron E, Garay MV, Starkey TW, Gianani R, et al. (2005) Recapitulation of elements of embryonic development in adult mouse pancreatic regeneration. Gastroenterology 128: 728–741. 22. Desai BM, Oliver-Krasinski J, De Leon DD, Farzad C, Hong N, et al. (2007) Preexisting pancreatic acinar cells contribute to acinar cell, but not islet beta cell, regeneration. J Clin Invest 117: 971–977. 23. Strobel O, Dor Y, Alsina J, Stirman A, Lauwers G, et al. (2007) In vivo lineage tracing defines the role of acinar-to-ductal transdifferentiation in inflammatory ductal metaplasia. Gastroenterology 133: 1999–2009. Acute Pancreatitis and Pancreatic Cancer 24. Zhu L, Shi G, Schmidt CM, Hruban RH, Konieczny SF (2007) Acinar cells contribute to the molecular heterogeneity of pancreatic intraepithelial neoplasia. Am J Pathol 171: 263–273. 25. Lesina M, Kurkowski MU, Ludes K, Rose-John S, Treiber M, et al. (2011) Stat3/Socs3 activation by IL-6 transsignaling promotes progression of pancreatic intraepithelial neoplasia and development of pancreatic cancer. Cancer Cell 19: 456–469. 26. Ishiwata T, Kudo M, Onda M, Fujii T, Teduka K, et al. (2006) Defined localization of nestin-expressing cells in L-arginine-induced acute pancreatitis. Pancreas 32: 360–368. 27. Esni F, Stoffers DA, Takeuchi T, Leach SD (2004) Origin of exocrine pancreatic cells from nestin-positive precursors in developing mouse pancreas. Mech Dev 121: 15–25. 28. Ebert M, Yokoyama M, Ishiwata T, Friess H, Buchler MW, et al. (1999) Alteration of fibroblast growth factor and receptor expression after acute pancreatitis in humans. Pancreas 18: 240–246. 29. Fendrich V, Esni F, Garay MV, Feldmann G, Habbe N, et al. (2008) Hedgehog signaling is required for effective regeneration of exocrine pancreas. Gastroen- terology 135: 621–631. 30. Scholz A, Heinze S, Detjen KM, Peters M, Welzel M, et al. (2003) Activated signal transducer and activator of transcription 3 (STAT3) supports the malignant phenotype of human pancreatic cancer. Gastroenterology 125: 891–905. 31. Ji B, Tsou L, Wang H, Gaiser S, Chang DZ, et al. (2009) Ras activity levels control the development of pancreatic diseases. Gastroenterology 137: 1072–1082, 1082 e1071–1076. 32. Logsdon CD, Ji B (2009) Ras activity in acinar cells links chronic pancreatitis and pancreatic cancer. Clin Gastroenterol Hepatol 7: S40–43. 33. Campbell PJ, Yachida S, Mudie LJ, Stephens PJ, Pleasance ED, et al. (2010) The patterns and dynamics of genomic instability in metastatic pancreatic cancer. Nature 467: 1109–1113. 34. Yachida S, Jones S, Bozic I, Antal T, Leary R, et al. (2010) Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature 467: 1114–1117. 35. Gu G, Dubauskaite J, Melton DA (2002) Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and are distinct from duct progenitors. Development 129: 2447–2457. PLoS ONE | www.plosone.org 7 November 2011 | Volume 6 | Issue 11 | e27725