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Molekularbiologische Grundlagen der Gastroenterologie pp 61–68Cite as

Molecular Biology of Pancreatic Cancer

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Abstract

The mammalian exocrine pancreas consists of acinar cells that synthesize and secrete digestive enzymes and duct cells that secrete bicarbonate rich fluid. Pancreatic exocrine function is regulated by gastrointestinal hormones, neurotransmitters, islet cell hormones such as insulin, and polypeptide growth factors. Under normal physiological conditions in the adult, there is a relatively low level of pancreatic acinar and duct cell proliferation, and proper progression through the cell cycle is assured by the presence of functioning protooncogenes and tumor suppressor genes. However, in conjunction with a variety of cellular and molecular perturbations in growth control mechanisms, the pancreas may give rise to a variety of malignancies. These malignancies may originate in any of the pancreatic cell types, leading to ductal carcinomas, acinar cell carcinomas, or islet cell tumors. Conceivably, some of these cancers may arise from a pancreatic stem cell that has the potential to acquire the characteristics of any of the above cell types. Alternatively, a given pancreatic cancer may appear to be a ductal carcinoma but may have arisen as a result of malignant transformation in another pancreatic cell which has acquired the duct cell phenotype.

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References

  1. Massague J, Pandiella A (1993) Membrane-anchored growth factors. Annu Rev Biochem 62:515–541.

    Article  PubMed  CAS  Google Scholar 

  2. Fen Z, Dhadly MS, Yoshizumi M, Hilkert RJ, Quertermous T, Eddy RL, Hows TB, Lee M-E (1993) Structural organization and chromosomal assignment of the gene encoding the human heparin-binding epidermal growth factor-like growth factor/diphteria toxin receptor. Biochemistry 32:7932–7938.

    Article  PubMed  CAS  Google Scholar 

  3. Plowman GD, Green JM, McDonald VL, Neubauer MG, Disteche CM, Todaro GJ, Shoyab M (1990) The amphiregulin gene encodes a novel epidermal growth factor-related protein with tumorinhibitory activity. Mol Cell Biol 10:1969–1981.

    PubMed  CAS  Google Scholar 

  4. Johnson GR, Saeki T, Gordon AW, Shoyab M, Salomon DS, Stromberg K (1992) Autocrine action of amphiregulin in a colon carcinoma cell line and immunocytochemical localization of amphiregulin in human colon. J Cell Biol 10:1969–1981.

    Google Scholar 

  5. Korc M, Haussler CA, Trookman NS (1987) Divergent effects of epidermal growth factor and transforming growth factors on a human endometrial carcinoma cell line. Cancer Res 47:4909–4914.

    PubMed  CAS  Google Scholar 

  6. Barrandon Y, Green H (1987) Cell migration is essential for sustained growth of keratinocyte colonies: the roles of transforming growth factor-α and epidermal growth factor. Cell 50:1131–1137.

    Article  PubMed  CAS  Google Scholar 

  7. Korc M, Chandrasekar B, Shah GN (1991) Differential binding and biological activities of epidermal growth factor and transforming growth factor a in a human pancreatic cancer cell line. Cancer Res 51:6243–6249.

    PubMed  CAS  Google Scholar 

  8. Gan BS, Hollenberg MD, MacCannell KL, Lederis K, Winkler ME, Derynck R (1987) Distinct vascular actions of epidermal growth factor-urogastrone and transforming growth factor-α. J Pharmacol Exp Ther 242:331–337.

    PubMed  CAS  Google Scholar 

  9. Yang SG, Ahmad S, Wong NC, Hollenberg MD (1994) Ligand binding characterization and molecular analysis of distinct epidermal growth factor-urogastrone receptors in cultured smooth muscle and epithelial cells from guinea pig intestine. Mol Pharmacol 46:256–265.

    PubMed  CAS  Google Scholar 

  10. Smith JJ, Derynck R, Korc M (1987) Production of transforming growth factor α in human pancreatic cancer cells: evidence for a superagonist autocrine cycle. Proc Natl Acad Sci USA 84:7567–7570.

    Article  PubMed  CAS  Google Scholar 

  11. Kobrin MS, Funatomi H, Friess H, Buchler MW, Stathis P, Korc M (1994) Induction and expression of heparin-binding EGF-like growth factor in human pancreatic cancer. Biochem Biophys Res Commun 202:1705–1709.

    Article  PubMed  CAS  Google Scholar 

  12. Barton CM, Hall PA, Hughes CM, Gullick WJ, Lemoine NR (1991) Transforming growth factor alpha and epidermal growth factor in human pancreatic cancer. J Pathol 163:111–116.

    Article  PubMed  CAS  Google Scholar 

  13. Korc M, Chandrasekar B, Yamanaka Y, Friess H, Buchler M, Beger HG (1992) Overexpression of the epidermal growth factor receptor in human pancreatic cancer is associated with concomitant increases in the levels of epidermal growth factor and transforming growth factor alpha. J Clin Invest 90:1352–1360.

    Article  PubMed  CAS  Google Scholar 

  14. Ebert M, Yokoyama M, Kobrin MS, Friess H, Lopez ME, Buchler MW, Johnson GR, Korc M (1994) Induction and expression of amphiregulin in human pancreatic cancer. Cancer Res 54:3959–3962.

    PubMed  CAS  Google Scholar 

  15. Yamanaka Y, Friess H, Kobrin MS, Buchler M, Beger HG, Korc M (1993) Coexpression of epidermal growth factor receptor and ligands in human pancreatic cancer is associated with enhanced tumor aggressiveness. Anticancer Res 13:565–570.

    PubMed  CAS  Google Scholar 

  16. Schlessinger J, Ullrich A (1992) Growth factor signaling by receptor tyrosine kinases. Neuron 9:383–391.

    Article  PubMed  CAS  Google Scholar 

  17. Prigent SA, Lemoine NR. The type 1 (EGFR-related) family of growth factor receptors and their ligands (1992) Prog Growth Factor Res 4:1-24.

    Google Scholar 

  18. Moriai T, Kobrin MS, Korc M. Cloning of a variant epidermal growth factor receptor from a human pancreatic cancer cell line (1993) Biochem Biophys Res Commun 91:1034–1039.

    Article  Google Scholar 

  19. Moriai T, Kobrin MS, Hope C, Speck L, Korc M (1994) A variant epidermal growth factor receptor exhibits altered type α transforming growth factor binding and transmembrane signaling. Proc Natl Acad Sci USA 91:10217–10221.

    Article  PubMed  CAS  Google Scholar 

  20. Pawson T, Schlessinger J (1993) SH2 and SH3 domains. Curr Biol 3:434–442.

    Article  PubMed  CAS  Google Scholar 

  21. Cadena DL, Gill GN (1992) Receptor tyrosine kinases. FASEB J 6:2332–2337.

    PubMed  CAS  Google Scholar 

  22. Ahn AG. The MAP kinase cascade (1993) Discovery of a new signal transduction pathway. Mol Cell Biochem 127:201–209.

    Article  Google Scholar 

  23. Soltoff SP, Carraway III KL, Prigent SA, Gullick WG, Cantley LC (1994) ErbB3 is involved in activation of phosphatidylinositol 3-kinase by epidermal growth factor. Mol Cell Biol 14:3550–3558.

    PubMed  CAS  Google Scholar 

  24. Lemoine NR, Hughes CM, Barton CM, Poulsom R, Jeffery RE, Kloppel G, Hall PA, Gullick WJ (1992) The epidermal growth factor receptor in human pancreatic cancer. J Pathol 166:7–12.

    Article  PubMed  CAS  Google Scholar 

  25. Yamanaka Y, Friess H, Kobrin MS, Buchler M, Kunz J, Beger HG, Korc M (1993) Overexpression of HER-2/neu oncogene in human pancreatic carcinoma. Human Pathol 24:1127–1134.

    Article  CAS  Google Scholar 

  26. Lemoine NR, Lobresco M, Leung H, Barton C, Hughes CM, Prigent SA, Gullick WJ, Klöppel G (1992) The erbB-3 gene in human pancreatic cancer. J Pathol 168:269–273.

    Article  PubMed  CAS  Google Scholar 

  27. Mason IJ (1994) The ins and outs of fibroblast growth factors. Cell 78:547–552.

    Article  PubMed  CAS  Google Scholar 

  28. Yamanaka Y, Friess H, Buchler M, Beger HG, Uchida E, Onda M, Kobrin MS, Korc M (1993) Overexpression of acidic and basic fibroblast growth factors in human pancreatic cancer correlates with advanced tumor stage. Cancer Res 53:5289–5296.

    PubMed  CAS  Google Scholar 

  29. Jaye M, Schlessinger J, Dionne C (1992) Fibroblast growth factor receptor tyrosine kinases: molecular analysis and signal transduction. Biochim Biophys Acta 1135:185–199.

    Article  PubMed  CAS  Google Scholar 

  30. Kobrin MS, Yamanaka Y, Friess H, Lopez ME, Korc M (1993) Aberrant expression of the type I fibroblast growth factor receptor in human pancreatic adenocarcinomas. Cancer Res 53:4741–4744.

    PubMed  CAS  Google Scholar 

  31. Kingsley DM (1994) The TGF-β superfamily: new members, new receptors, and new genetic tests of function in different organisms. Genes Dev 8:133–146.

    Article  PubMed  CAS  Google Scholar 

  32. Yamanaka Y, Friess H, Buchler M, Beger HG, Gold LI, Korc M (1993) Synthesis and expression of transforming growth factor beta-1, beta-2, and beta-3 in the endocrine and exocine pancreas. Diabetes 42:746–756.

    Article  PubMed  CAS  Google Scholar 

  33. Friess H, Yamanaka Y, Buchler M, Ebert M, Beger HG, Gold LI, Korc M (1993) Enhanced expression of transforming growth factor-beta isoforms in human pancreatic cancer correlates with decreased survival. Gastroenterology 105:1846–1856.

    PubMed  CAS  Google Scholar 

  34. Lin HY, Lodish HF (1993) Receptors for the TGF-beta superfamily: multiple polypeptides and serine/threonine kinases. Trends Cell Biol 3:14–19.

    Article  PubMed  CAS  Google Scholar 

  35. Wrana JL, Attisano L, Carcamo J, Zentella A, Doody J, Laiho M, Wang XF, Massague J (1992) TGF beta signals through a heteromeric protein kinase receptor complex. Cell 71:1003–1014.

    Article  PubMed  CAS  Google Scholar 

  36. Friess H, Yamanaka Y, Buchler M, Beger HG, Kobrin MS, Baldwin RL, Korc M (1993) Enhanced expression of the type II transforming growth factor β receptor in human pancreatic cancer cells without alteration of type III receptor expression. Cancer Res 53:2704–2707.

    PubMed  CAS  Google Scholar 

  37. Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M (1988) Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell 53:549–554.

    Article  PubMed  CAS  Google Scholar 

  38. Grunewald K, Lyons J, Fröhlich A, Feichtinger H, Weger RA, Schwab G, Janssen JWG, Bartram CR (1989) High frequency of Ki-ras codon 12 mutations in pancreatic adenocarcinomas. Int J Cancer 43:1037–1041.

    Article  PubMed  CAS  Google Scholar 

  39. Caldas C, Hahn SA, Hruban RH, Redston MS, Yeo CJ, Kern SE (1994) Detection of K-ras mutations in the stool of patients with pancreatic adenocarcinoma and pancreatic ductal hyperplasia. Cancer Res 54:3568–3573.

    PubMed  CAS  Google Scholar 

  40. Pellegata NS, Sessa F, Rneut B, Bonato B, Leone BE, Solda E, Ranzani GN (1994) K-ras and p 53 gene mutation in pancreatic cancer: ductal and nonductal tumors progress through different genetic lesions. Cancer Res 54:1556–1560.

    PubMed  CAS  Google Scholar 

  41. Barton CM, Staddon SL, Hughes CM, Hall PA, O’Sullivan C, Kloppel G et al. (1991) Abnormalities of the p 53 tumour suppressor gene in human pancreatic cancer. Br J Cancer 64:1076–1082.

    Article  PubMed  CAS  Google Scholar 

  42. Casey G, Yamanaka Y, Friess H, Kobrin MS, Lopez ME, Buchler M, Beger HG, Korc M (1993) p 53 Mutations are common in pancreatic cancer and are absent in chronic pancreatitis, Cancer Let.

    Google Scholar 

  43. Wang P, Reed M, Wang Y, Mayr G, Stenger JE, Anderson ME, Schwedes JF, Tegtmeyer P (1994) p53 domains: structure, oligomerization, and transformation. Mol Cell Biol 14:5182–5191.

    PubMed  CAS  Google Scholar 

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Authors
  1. M. Korc
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Editor information

Editors and Affiliations

  1. Chirurgische Klinik I, Universität Ulm, Steinhövelstr. 9, 89075, Ulm, Deutschland

    Hans G. Beger

  2. Abteilung Gastroenterologie, Medizinische Hochschule Hannover, Konstanty-Gutschow-Str. 8, 30625, Hannover, Deutschland

    Michael P. Manns

  3. I. Medizinische Universitäts-Klinik, Martinistr. 52, 20251, Hamburg, Deutschland

    Heiner Greten

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© 1995 Springer-Verlag Berlin Heidelberg

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Korc, M. (1995). Molecular Biology of Pancreatic Cancer. In: Beger, H.G., Manns, M.P., Greten, H. (eds) Molekularbiologische Grundlagen der Gastroenterologie. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-79782-8_6

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  • DOI: https://doi.org/10.1007/978-3-642-79782-8_6

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-59325-6

  • Online ISBN: 978-3-642-79782-8

  • eBook Packages: Springer Book Archive

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