Transgenic models of pancreatic cancer

  • Andrew M. Lowy
Review Article


Pancreatic Cancer Pancreatic Duct Acinar Cell Human Pancreatic Cancer Exocrine Pancreas 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Jemal A, Thomas A, Murray T, Thun M. Cancer Statistics. The CA Journal 1996;52:23–47.Google Scholar
  2. 2.
    Sohn TA, Yeo CJ, Cameron JL, et al. Resected adenocarcinoma of the pancreas-616 patients: Results, outcomes and prognostic indicators. J Gastrointest Surg 2000;4:567–579.PubMedCrossRefGoogle Scholar
  3. 3.
    Warshaw AL, Fernandez-del Castillo C. Pancreatic carcinoma. N Engl J Med 1992;326:455–65.PubMedCrossRefGoogle Scholar
  4. 4.
    Caldas C, Kern SE. K-ras mutations and pancreatic adenocarcinoma. Int J Pancreatol 1995;18:1–6.PubMedCrossRefGoogle Scholar
  5. 5.
    Simon B, Weinel R, Hohne M, Kern SE. Frequent alterations of the tumor suppressors p53 and DCC in human pancreatic adenocarcinoma. Gastroenterology 1994;106:1645–1651.PubMedGoogle Scholar
  6. 6.
    Caldas C, Hahn SA, da Costa LT, et al. Frequent somatic mutations and homozygous deletions of the p16(MTS1) gene in pancreatic adenocarcinoma. Nature Genetics 1994;8:27–32.PubMedCrossRefGoogle Scholar
  7. 7.
    Hahn SA, Schutte M, Hoque AT, et al. DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science 1996;272:350–353.CrossRefGoogle Scholar
  8. 8.
    Horii A, Nakatsuru S, Miyoshi, et al. Frequent somatic mutations of the APC gene in human pancreatic cancer. Cancer Res 1992;52:6696–6698.PubMedGoogle Scholar
  9. 9.
    Lal G, Liu G, Schmocker B, et al. Inherited predisposition to pancreatic adenocarcinoma: Role of family history and germ-line p16, BRCA1 and BRCA2 mutations. Cancer Res 2000;60:409–416.PubMedGoogle Scholar
  10. 10.
    Seymour AB, Hruban RH, Redston M, et al. Allelotype of pancreatic adenocarcinoma. Cancer Res 1994;54:2761–2764.PubMedGoogle Scholar
  11. 11.
    Longnecker DS. The azaserine-induced model of pancreatic carcinogenesis in rats, in Experimental pancreatic carcinogenesis, Scarpelli DG, Reddy JK, Longnecker DS, eds. CRC Press Boca Raton: 1987:117–130.Google Scholar
  12. 12.
    Rivera JA, Graeme-Cook F, Werner J, Graggen K, Rustgi AK, Rattner DW, Warshaw AL, Fernandez-del Castillo C. A rat model of pancreatic ductal adenocarcinoma: Targeting chemical carcinogens. Surgery 1997;122:82–90PubMedCrossRefGoogle Scholar
  13. 13.
    Graggen K, Limenez R, Werner J, Graeme-Cook F, Warshaw A, Fernandez-del Castillo C. Mutations of the K-ras but not the H-ras gene are involved in the carcinogenesis of DMBA-induced pancreatic ductal adenocarcinoma in rats. Pancreas 1998;17:460–465.Google Scholar
  14. 14.
    Scarpelli DG, Rao MS. Transplantable ductal adenocarcinoma of the Syrian hamster pancreas. Cancer Res 1979;39:452–458.PubMedGoogle Scholar
  15. 15.
    Cerny WL, Mangold KA, Scarpelli DG. K-ras mutation is an early event in pancreatic duct carcinogenesis in the Syrian Golden hamster. Cancer Res 1992;52:4507–4513.PubMedGoogle Scholar
  16. 16.
    Standop J, Schneider MB, Ulrich A, Pur PM. Experimental animal models in pancreatic carcinogenesis: Lessons for human pancreatic cancer. Dig Dis 2001;19:24–31.PubMedCrossRefGoogle Scholar
  17. 17.
    Chang KW, Laconi S, Mangold KA, Hubchak S, Scarpelli DG. Multiple genetic alterations in hamster ductal pancreatic adenocarcinomas. Cancer Res 1995;55:2560–2568.PubMedGoogle Scholar
  18. 18.
    Corbett TH, Roberts BJ, Leopold WR, Peckham JC, Wilkoff LJ, Griswold Jr. DP, Schabel Jr. FM. Induction and chemotherapeutic response of two transplantable ductal adenocarcinomas of the pancreas in C57BL/6 mice. Cancer Res 1984;44:717–726.PubMedGoogle Scholar
  19. 19.
    Brembeck FH, Moffett, Wang TC, Rustgi AK. The keratin 19 promoter is potent for cell-specific targeting of genes in transgenic mice. Gastroenterology 2001;120:1720–1728.PubMedCrossRefGoogle Scholar
  20. 20.
    Jonsson J, Carlsson L, Edlund T. Insulin-promoter-factor 1 is required for pancreas development in mice. Nature 1994;371:606–609.PubMedCrossRefGoogle Scholar
  21. 21.
    St-Onge L, Sosa-Pineda B, Chowdhury K, Mansouri A, Gruss P. Pax is required for differentiation of glucagonproducing α-cells in mouse pancreas. Nature 1997;387:406–409.PubMedCrossRefGoogle Scholar
  22. 22.
    Kawaguchi Y, Cooper B, Gannon M, Ray M, MacDonald RJ, Wright CV. The role of transcriptional regulator Ptfla inconverting intestinal to pancreatic progenitors. Nat Genet 2002;32:85–86.CrossRefGoogle Scholar
  23. 23.
    Sternberg N, Hamilton D. Bacteriophage P1 site-specific recombination. I. Recombination between LoxP sites. J Mol Biol 1981;150:467–486.PubMedCrossRefGoogle Scholar
  24. 24.
    Sauer B, Henderson N. Site-specific DNA recombination in mammalian cells by the cre recombinase of bacteriophage P1. Proc Natl Acad Sci 1988;85:5166–5170.PubMedCrossRefGoogle Scholar
  25. 25.
    Fiering S, Kim CG, Epner EM, Groudine M. An in-out strategy using gene targeting and FLP recombinase for the functional dissection of complex DNA regulatory elements: Analysis of the β-globin locus control region. Proc Natl Acad Sci 1993;90:8469–8473.PubMedCrossRefGoogle Scholar
  26. 26.
    Johnson L, Mercer K, Greenbaum D, Bronson RT, Crowley D, Tuveson DA, Jacks T. Somatic activation of the K-ras Oncogene casues early onsetlung cancer in mice. Nature 2001;410:1111–1116.PubMedCrossRefGoogle Scholar
  27. 27.
    Burein MM, Malley BW, Tsai SY. A regulatory system for target gene expression. Frontiers in Bioscience 1998;3:c1–7.Google Scholar
  28. 28.
    Ornitz DM, Hammer RE, Messing A, Palmiter RD, Brinster RL. Pancreatic neoplasia induced by SV40 T-antigen expression in acinar cells of transgenic mice. Science 1987;238:188–193.PubMedCrossRefGoogle Scholar
  29. 29.
    Ceci JD, Kovatch RM, Swing DA, et al. Transgenic mice carrying a murine amylase 2.2/SV40T antigen fusion gene develop pancreatic acinar cell and stomach carcinomas. Oncogene 1991;6:323–332.PubMedGoogle Scholar
  30. 30.
    Ramel S, Sanchez CA, Schimke MK, Neshat K, Cross SM, Raskind WH, Reid BJ. Inactivation of p53 and the development of tetraploidy in the elastase-SV40 T antigen transgenic mouse pancreas. Pancreas 1995;11:213–222.PubMedCrossRefGoogle Scholar
  31. 31.
    Asa SL, Lee YC, Drucker DJ. Development of colonic and pancreatic endocrine tumours in mice expressing a glucagon-SV40 T antigen transgene. Virchows Archives 1996;427:595–606.Google Scholar
  32. 32.
    MacDonald RJ, Swift GH. Transgenic analysis of pancreatic function and development in The Pancreas: Biology, Pathobiology and Disease 2nd Ed. Go VLM, Dimagno EP, Gardner JD, Lebenthal E, Reber HA, Scheele, GA, eds. Raven Press. New York, NY 1993.Google Scholar
  33. 33.
    Clarke AR, Cummings MC, Harrison DJ. Interaction between murine germline mutations in p53 and APC predisposes to pancreatic neoplasia but not to increased intestinal malignancy. Oncogene 1995;11:1913–1920.PubMedGoogle Scholar
  34. 34.
    Quaife CJ, Pinkert CA, Ornitz DM, Palmiter RD, Brinster RL. Pancreatic neoplasia induced by ras expression in acinar cells of transgenic mice. Cell 1987;48:1023–1034.PubMedCrossRefGoogle Scholar
  35. 35.
    Lebenthal E, Lev R, Lee PC. Prenatal and postnatal development of the human exocrine pancreas. in: The exocrine pancreas; biology, pathobiology, and diseases. Go VLW, et al. eds. Raven Press: New York; 1986; 33–43.Google Scholar
  36. 36.
    Sandgren EP, Quaife CJ, Paulovich AG, Palmiter RD, Brinster RL. Pancreatic tumor pathogenesis reflects the causative genetic lesion. Proc Natl Acad Sci USA 1991;88:93–97.PubMedCrossRefGoogle Scholar
  37. 37.
    Wagner M, Luhrs, H, Kloppel G, Adler G, Schmid RM. Malignant transformation of duct-like cells originating from acini in transforming growth factor I transgenic mice. Gastroenterology 1998;115:1254–1262.PubMedCrossRefGoogle Scholar
  38. 38.
    Vassar R, Hutton ME, Fuchs E. Transgenic overexpression of transforming growth factor alpha bypasses the need for c-H-ras mutations in mouse skin tumorigenesis. Mol Cell Biol 1992;12:4643–4653.PubMedGoogle Scholar
  39. 39.
    Ornitz DM, Palmiter RD, Hammer RE, Brinster RL, Swift GH, MacDonald RJ. Specific expression of an elastase-human growth hormone fusion gene in pancreatic acinar cells of transgenic mice. Nature 1985;313:600–603.PubMedCrossRefGoogle Scholar
  40. 40.
    Dusetti NJ, Vasseur S, Ortiz EM, Romeo H, Dagorn JC, Burrone O, Iovanna JL. The pancreatitis-associated protein I promoter allows targeting to the pancreas of a foreign gene, whose expression is up-regulated during pancreatic inflammation. J Biol Chem 1997;272:5800–5804.PubMedCrossRefGoogle Scholar
  41. 41.
    Yamaoka T, Idehara C, Yano M, Matsushita T, Yamada T, Ii S, Moritani M, Hata J, Sugino H, Noji S, Itakura M. Hypoplasia of pancreatic islets in transgenic mice expressing activin receptor mutants. J Clin Invest 1998;102:294–301.PubMedCrossRefGoogle Scholar
  42. 42.
    von Herrath MG, Allison J, Miller JF, Oldstone MB. Focal expression of interleukin-2 does not break unresponsiveness to self (viral) antigen expressed in beta cells but enhances development of autoimmune disease (diabetes) after initiation of an anti-self immune response. J Clin Invest 1995;95:477–485.CrossRefGoogle Scholar
  43. 43.
    Mueller R, Krahl T, Sarvetnick N. Tissue-specific expression of interleukin-4 induces extracellular matrix accumulation and extravasation of B cells. Lab Invest 1997;76:117–128.PubMedGoogle Scholar
  44. 44.
    Mueller R, Lee MS, Sawyer SP, Sarvetnick N. Transgenic expression of interleukin 10 in the pancreas renders resistant mice susceptible to low dose streptozotocin-induced diabetes. J Autoimmun 1996;9:151–158.PubMedCrossRefGoogle Scholar
  45. 45.
    Gu D, Arnush M, Sawyer SP, Sarvetnick N. Transgenic mice expressing IFN-gamma in pancreatic beta-cells are resistant to streptozotocin-induced diabetes. Am J Physiol 1995;269(6 Pt 1):E1089–1094.PubMedGoogle Scholar
  46. 46.
    Grodsky GM, Ma YH, Cullen B, Sarvetnick N. Effect on insulin production sorting and secretion by major histocompatibility complex class II gene expression in the pancreatic beta-cell of transgenic mice. Endocrinology 1992;131:933–938.PubMedCrossRefGoogle Scholar
  47. 47.
    Wong S, Guerder S, Visintin I, Reich EP, Swenson KE, Flavell RA, Janeway Jr. CA. Expression of the co-stimulator molecule B7-1 in pancreatic beta-cells accelerates diabetes in the NOD mouse. Diabetes 1995;44:326–329.PubMedCrossRefGoogle Scholar
  48. 48.
    Sandgren EP, Luetteke NC, Palmiter RD, Brinster RL, Lee DC. Overexpression of TGF-I in transgenic mice: induction of epithelial hyperplasia, pancreatic metaplasia, and carcinoma of the breast. Cell 1990;61:1121–1135.PubMedCrossRefGoogle Scholar
  49. 49.
    Lee MS, Gu D, Feng L, et al. Accumulation of extracellular matrix and developmental dysregulation in the pancreas by transgenic production of transforming growth factorbeta 1. Am J Pathol 1995;147:42–52.PubMedGoogle Scholar
  50. 50.
    Ma YH, Landis C, Tchao N, et al. Constitutively active stimulatory G-protein alpha (s) in beta-cells of transgenic mice causes counterregulation of the increased adenosine 3′,5′-monophosphate and insulin secretion. Endocrinology 1994;134:42–47.PubMedCrossRefGoogle Scholar
  51. 51.
    Bamber BA, Masters BA, Hoyle GW, Brinster RL, Palmiter RD. Leukemia inhibitory factor induces neurotransmitter switching in transgenic mice. Proc Nat Acad Sci 1994;91:7839–7843.PubMedCrossRefGoogle Scholar
  52. 52.
    Picarella DE, Kratz A, Li CB, Ruddle NH, Flavell RA. Insulinitis in transgenic mice expressing tumor necrosis factor beta (lymphotoxin) in the pancreas. Proc Nat Acad Sci 1992;89:10,036–10,040.CrossRefGoogle Scholar
  53. 53.
    Asa SL, Lee YC, Drucker DJ. Development of colonic and pancreatic endocrine tumours in mice expressing a glucagon-SV40 T antigen transgene. Virchows Archives 1996;427:595–606.Google Scholar

Copyright information

© Humana Press Inc 2003

Authors and Affiliations

  1. 1.Division of Surgical OncologyUniversity of Cincinnati College of MedicineCincinnati

Personalised recommendations