Gastroenterology
Volume 138, Issue 3 , Pages 1189-1199.e2 , March 2010

NFAT-Induced Histone Acetylation Relay Switch Promotes c-Myc-Dependent Growth in Pancreatic Cancer Cells

  • Alexander Köenig

      Affiliations

    • Department of Gastroenterology and Endocrinology, Philipps-University of Marburg, Marburg, Germany
  • ,
  • Thomas Linhart

      Affiliations

    • Department of Gastroenterology and Endocrinology, Philipps-University of Marburg, Marburg, Germany
  • ,
  • Katrin Schlengemann

      Affiliations

    • Department of Gastroenterology and Endocrinology, Philipps-University of Marburg, Marburg, Germany
  • ,
  • Kristina Reutlinger

      Affiliations

    • Department of Gastroenterology and Endocrinology, Philipps-University of Marburg, Marburg, Germany
  • ,
  • Jessica Wegele

      Affiliations

    • Department of Gastroenterology, University of Ulm, Ulm, Germany
  • ,
  • Guido Adler

      Affiliations

    • Department of Gastroenterology, University of Ulm, Ulm, Germany
  • ,
  • Garima Singh

      Affiliations

    • Department of Gastroenterology and Endocrinology, Philipps-University of Marburg, Marburg, Germany
  • ,
  • Leonie Hofmann

      Affiliations

    • Department of Gastroenterology and Endocrinology, Philipps-University of Marburg, Marburg, Germany
  • ,
  • Steffen Kunsch

      Affiliations

    • Department of Gastroenterology and Endocrinology, Philipps-University of Marburg, Marburg, Germany
  • ,
  • Thomas Büch

      Affiliations

    • Walther-Straub-Institute of Pharmacology and Toxicology, Ludwig-Maximilian University, Munich, Germany
  • ,
  • Eva Schäfer

      Affiliations

    • Walther-Straub-Institute of Pharmacology and Toxicology, Ludwig-Maximilian University, Munich, Germany
  • ,
  • Thomas M. Gress

      Affiliations

    • Department of Gastroenterology and Endocrinology, Philipps-University of Marburg, Marburg, Germany
  • ,
  • Martin E. Fernandez–Zapico

      Affiliations

    • Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, Minnesota
  • ,
  • Volker Ellenrieder

      Affiliations

    • Department of Gastroenterology and Endocrinology, Philipps-University of Marburg, Marburg, Germany
    • Corresponding Author InformationReprint requests Address requests for reprints to: Volker Ellenrieder, MD, Department of Gastroenterology and Endocrinology, Philipps-University of Marburg, Baldingerstrasse, 35043 Marburg, Germany

Received 28 June 2009 ,Accepted 29 October 2009.

References 

  1. Almendral JM, Sommer D, Macdonald-Bravo H, et al. Complexity of the early genetic response to growth factors in mouse fibroblasts. Mol Cell Biol. 1988;8:2140–2148
  2. Bravo R. Growth factor-responsive genes in fibroblasts. Cell Growth Differ. 1990;1:305–309
  3. Lee MH, Yang HY. Regulators of G1 cyclin-dependent kinases and cancers. Cancer Metastasis Rev. 2003;22:435–449
  4. Murphy LO, MacKeigan JP, Blenis J. A network of immediate early gene products propagates subtle differences in mitogen-activated protein kinase signal amplitude and duration. Mol Cell Biol. 2004;24:144–153
  5. Chen CR, Kang Y, Siegel PM, et al. E2F4/5 and p107 as Smad cofactors linking the TGF-β receptor to c-myc repression. Cell. 2002;110:19–32
  6. Sng JC, Taniura H, Yoneda Y. A tale of early response genes. Biol Pharm Bull. 2004;27:606–612
  7. Yordy JS, Muise-Helmericks RC. Signal transduction and the Ets family of transcription factors. Oncogene. 2000;19:6503–6513
  8. Herold S, Herkert B, Eilers M. Facilitating replication under stress: an oncogenic function of MYC?. Nat Rev Cancer. 2009;9:441–444
  9. Murphy LO, Blenis J. MAPK signal specificity: the right place at the right time. Trends Biochem Sci. 2006;31:268–275
  10. Hsu T, Trojanowska M, Watson DK. Ets proteins in biological control and cancer. J Cell Biochem. 2004;91:896–903
  11. Thiel G, Cibelli G. Regulation of life and death by the zinc finger transcription factor Egr-1. J Cell Physiol. 2002;193:287–292
  12. Jochum W, Passegue E, Wagner EF. AP-1 in mouse development and tumorigenesis. Oncogene. 2002;20:2401–2412
  13. Eilers M, Eisenman RN. Myc's broad reach. Genes Dev. 2008;22:2755–2766
  14. Ghaneh P, Costello E, Neoptolemos JP. Biology and management of pancreatic cancer. Postgrad Med J. 2008;84:478–497
  15. Schneider G, Siveke JT, Eckel F, et al. Pancreatic cancer: basic and clinical aspects. Gastroenterology. 2005;128:1606–1625
  16. Buchholz M, Schatz A, Wagner M, et al. Overexpression of c-myc in pancreatic cancer caused by ectopic activation of NFATc1 and the Ca2+/calcineurin signaling pathway. EMBO J. 2006;25:3714–3724
  17. Buck A, Buchholz M, Wagner M, et al. The tumor suppressor KLF11 mediates a novel mechanism in transforming growth factor β-induced growth inhibition that is inactivated in pancreatic cancer. Mol Cancer Res. 2006;4:861–872
  18. Ellenrieder V, Zhang JS, Kaczynski J, et al. Signaling disrupts mSin3A binding to the Mad1-like Sin3-interacting domain of TIEG2, an Sp1-like repressor. EMBO J. 2002;21:2451–2460
  19. Baubet V, Le Mouellic H, Campbell AK, et al. Chimeric green fluorescent protein-aequorin as bioluminescent Ca2+ reporters at the single-cell level. Proc Natl Acad Sci U S A. 2000;97:7260–7265
  20. Jones K, Hibbert F, Keenan M. Glowing jellyfish, luminescence and a molecule called coelenterazine. Trends Biotechnol. 1999;17:477–481
  21. Fernandez-Zapico ME, Gonzalez-Paz NC, Weiss E, et al. Ectopic expression of VAV1 reveals an unexpected role in pancreatic cancer tumorigenesis. Cancer Cell. 2005;7:39–49
  22. Dunn KL, Espino PS, Drobic B, et al. Ras-MAPK signal transduction pathway, cancer and chromatin remodeling. Biochem Cell Biol. 2005;83:1–14
  23. Yagi K, Furuhashi M, Aoki H, et al. c-myc Is a downstream target of the Smad pathway. J Biol Chem. 2002;277:854–861
  24. Rao A, Luo C, Hogan PG. Transcription factors of the NFAT family: regulation and function. Annu Rev Immunol. 1997;15:707–747
  25. Wang L, Tang Y, Cole PA, et al. Structure and chemistry of the p300/CBP and Rtt109 histone acetyltransferases: implications for histone acetyltransferase evolution and function. Curr Opin Struct Biol. 2008;18:741–747
  26. Crabtree GR, Olson EN. NFAT signaling: choreographing the social lives of cells. Cell. 2002;109:67–79
  27. Neal JW, Clipstone NA. A constitutively active NFATc1 mutant induces a transformed phenotype in 3T3-L1 fibroblasts. J Biol Chem. 2003;278:17246–17254
  28. Buchholz M, Ellenrieder V. An emerging role for Ca2+/calcineurin/NFAT signaling in cancerogenesis. Cell Cycle. 2007;6:16–19
  29. Robbs BK, Cruz AL, Werneck MB, et al. Dual roles for NFAT transcription factor genes as oncogenes and tumor suppressors. Mol Cell Biol. 2008;28:7168–7181
  30. Jauliac S, López-Rodriguez C, Shaw LM, et al. The role of NFAT transcription factors in integrin-mediated carcinoma invasion. Nat Cell Biol. 2002;4:540–544

 Conflicts of interest The authors disclose no conflicts.

 Funding Supported by the Deutsche Forschungsgemeinschaft (DFG, SFB-TR17; to V.E., A.G., and J.M.) and the Max Eder program of the German Cancer Research Foundation (Deutsche Krebshilfe, 70-3022-El I; to V.E.) and by the Miles and Shirley Fiterman Center for Digestive Diseases, Division of Gastroenterology and Hepatology, Division of Oncology Research, Mayo Clinic Cancer Center, Mayo Clinic Pancreatic SPORE P50 CA102701 and CA136526 (to M.E.F.-Z.).

PII: S0016-5085(09)01942-8

doi: 10.1053/j.gastro.2009.10.045

Gastroenterology
Volume 138, Issue 3 , Pages 1189-1199.e2 , March 2010