Human Pathology
Volume 41, Issue 3 , Pages 358-365 , March 2010

Overexpression of cell division cycle 7 homolog is associated with gene amplification frequency in breast cancer

  • Matthias Choschzick, MD

      Affiliations

    • Institute of Pathology, University Medical Centre Hamburg-Eppendorf, 20246 Hamburg, Germany
  • ,
  • Annette Lebeau, MD

      Affiliations

    • Institute of Pathology, University Medical Centre Hamburg-Eppendorf, 20246 Hamburg, Germany
  • ,
  • Andreas H. Marx, MD

      Affiliations

    • Institute of Pathology, University Medical Centre Hamburg-Eppendorf, 20246 Hamburg, Germany
  • ,
  • Lars Tharun

      Affiliations

    • Institute of Pathology, University Medical Centre Hamburg-Eppendorf, 20246 Hamburg, Germany
  • ,
  • Luigi Terracciano, MD

      Affiliations

    • Institute of Pathology, Cantonal Hospital Basel, 4031 Basel, Switzerland
  • ,
  • Uwe Heilenkötter, MD

      Affiliations

    • Department of Gynaecology, Hospital Itzehoe, 25524 Itzehoe, Germany
  • ,
  • Fritz Jaenicke, MD

      Affiliations

    • Department of Gynaecology, University Medical Centre Hamburg-Eppendorf, 20246 Hamburg, Germany
  • ,
  • Carsten Bokemeyer, MD

      Affiliations

    • Department of Oncology, Hematology, Bone Marrow Transplantation with Section Pneumology, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany
  • ,
  • Ronald Simon, PhD

      Affiliations

    • Institute of Pathology, University Medical Centre Hamburg-Eppendorf, 20246 Hamburg, Germany
    • Corresponding Author InformationCorresponding author.
  • ,
  • Guido Sauter, MD

      Affiliations

    • Institute of Pathology, University Medical Centre Hamburg-Eppendorf, 20246 Hamburg, Germany
  • ,
  • Jörg Schwarz, MD

      Affiliations

    • Department of Gynaecology, University Medical Centre Hamburg-Eppendorf, 20246 Hamburg, Germany

Received 23 April 2009 ,Revised 25 June 2009 ,Accepted 4 August 2009.

References 

  1. Sclafani RA. Cdc7p-Dbf4p becomes famous in the cell cycle. J Cell Sci. 2000;113(Pt 12):2111–2117
  2. Kim JM, Yamada M, Masai H. Functions of mammalian Cdc7 kinase in initiation/monitoring of DNA replication and development. Mutat Res. 2003;532:29–40
  3. Masai H, Arai K. Cdc7 kinase complex: a key regulator in the initiation of DNA replication. J Cell Physiol. 2002;190:287–296
  4. Masai H, Taniyama C, Ogino K, et al. Phosphorylation of MCM4 by Cdc7 kinase facilitates its interaction with Cdc45 on the chromatin. J Biol Chem. 2006;281:39249–39261
  5. Tsuji T, Ficarro SB, Jiang W. Essential role of phosphorylation of MCM2 by Cdc7/Dbf4 in the initiation of DNA replication in mammalian cells. Mol Biol Cell. 2006;17:4459–4472
  6. Charych DH, Coyne M, Yabannavar A, et al. Inhibition of Cdc7/Dbf4 kinase activity affects specific phosphorylation sites on MCM2 in cancer cells. J Cell Biochem. 2008;104:1075–1086
  7. Montagnoli A, Tenca P, Sola F, et al. Cdc7 inhibition reveals a p53-dependent replication checkpoint that is defective in cancer cells. Cancer Res. 2004;64:7110–7116
  8. Yoshizawa-Sugata N, Ishii A, Taniyama C, Matsui E, Arai K, Masai H. A second human Dbf4/ASK-related protein, Drf1/ASKL1, is required for efficient progression of S and M phases. J Biol Chem. 2005;280:13062–13070
  9. Im JS, Lee JK. ATR-dependent activation of p38 MAP kinase is responsible for apoptotic cell death in cells depleted of Cdc7. J Biol Chem. 2008;283:25171–25177
  10. Kim JM, Kakusho N, Yamada M, Kanoh Y, Takemoto N, Masai H. Cdc7 kinase mediates claspin phosphorylation in DNA replication checkpoint. Oncogene. 2008;27:3475–3482
  11. Montagnoli A, Valsasina B, Croci V, et al. A Cdc7 kinase inhibitor restricts initiation of DNA replication and has antitumor activity. Nat Chem Biol. 2008;4:357–365
  12. Vanotti E, Amici R, Bargiotti A, et al. Cdc7 kinase inhibitors: pyrrolopyridinones as potential antitumor agents. 1. Synthesis and structure-activity relationships. J Med Chem. 2008;51:487–501
  13. Menichincheri M, Bargiotti A, Berthelsen J, et al. First Cdc7 kinase inhibitors: pyrrolopyridinones as potent and orally active antitumor agents. 2. Lead discovery. J Med Chem. 2009;
  14. Bonte D, Lindvall C, Liu H, Dykema K, Furge K, Weinreich M. Cdc7-Dbf4 kinase overexpression in multiple cancers and tumor cell lines is correlated with p53 inactivation. Neoplasia. 2008;10:920–931
  15. Clarke LE, Fountaine TJ, Hennessy J, et al. Cdc7 expression in melanomas, Spitz tumors and melanocytic nevi. J Cutan Pathol. 2009;36:433–438
  16. Kulkarni AA, Kingsbury SR, Tudzarova S, et al. Cdc7 kinase is a predictor of survival and a novel therapeutic target in epithelial ovarian carcinoma. Clin Cancer Res. 2009;
  17. Sauter G, Simon R, Hillan K. Tissue microarrays in drug discovery. Nat Rev Drug Discov. 2003;2:962–972
  18. Al-Kuraya K, Schraml P, Torhorst J, et al. Prognostic relevance of gene amplifications and coamplifications in breast cancer. Cancer Res. 2004;64:8534–8540
  19. Ruiz C, Seibt S, Al Kuraya K, et al. Tissue microarrays for comparing molecular features with proliferation activity in breast cancer. Int J Cancer. 2006;118:2190–2194
  20. Holst F, Stahl PR, Ruiz C, et al. Estrogen receptor alpha (ESR1) gene amplification is frequent in breast cancer. Nat Genet. 2007;39:655–660
  21. Simon R, Panussis S, Maurer R, et al. KIT (CD117)-positive breast cancers are infrequent and lack KIT gene mutations. Clin Cancer Res. 2004;10:178–183
  22. Matkovic B, Juretic A, Separovic V, et al. Immunohistochemical analysis of ER, PR, HER-2, CK 5/6, p63 and EGFR antigen expression in medullary breast cancer. Tumori. 2008;94:838–844
  23. Park K, Kwak K, Kim J, Lim S, Han S. c-myc Amplification is associated with HER2 amplification and closely linked with cell proliferation in tissue microarray of nonselected breast cancers. Hum Pathol. 2005;36:634–639
  24. Courjal F, Theillet C. Comparative genomic hybridization analysis of breast tumors with predetermined profiles of DNA amplification. Cancer Res. 1997;57:4368–4377
  25. Yoshida K, Takisawa H, Kubota Y. Intrinsic nuclear import activity of geminin is essential to prevent re-initiation of DNA replication in Xenopus eggs. Genes Cells. 2005;10:63–73
  26. Zimmer WE. Amplification of chicken actin genes during myogenesis. In:  Schimke RT editors. Gene amplification. Cold Spring Harbor (NY): Cold Spring Harbor Press; 1982;p. 137–146
  27. Schwed G, May N, Pechersky Y, Calvi BR. Drosophila minichromosome maintenance 6 is required for chorion gene amplification and genomic replication. Mol Biol Cell. 2002;13:607–620
  28. Cavaliere V, Bernardi F, Romani P, Duchi S, Gargiulo G. Building up the Drosophila eggshell: first of all the eggshell genes must be transcribed. Dev Dyn. 2008;237:2061–2072
  29. Spradling AC. The organization and amplification of two chromosomal domains containing Drosophila chorion genes. Cell. 1981;27:193–201
  30. Landis G, Tower J. The Drosophila chiffon gene is required for chorion gene amplification, and is related to the yeast Dbf4 regulator of DNA replication and cell cycle. Development. 1999;126:4281–4293
  31. Boskovic J, Coloma J, Aparicio T, et al. Molecular architecture of the human GINS complex. EMBO Rep. 2007;8:678–684
  32. Bauerschmidt C, Pollok S, Kremmer E, Nasheuer HP, Grosse F. Interactions of human Cdc45 with the Mcm2-7 complex, the GINS complex, and DNA polymerases delta and epsilon during S phase. Genes Cells. 2007;12:745–758
  33. Halazonetis TD, Gorgoulis VG, Bartek J. An oncogene-induced DNA damage model for cancer development. Science. 2008;319:1352–1355
  34. Ito S, Taniyami C, Arai N, Masai H. Cdc7 as a potential new target for cancer therapy. Drug News Perspect. 2008;21:481–488
  35. Bartek J, Bartkova J, Lukas J. DNA damage signalling guards against activated oncogenes and tumour progression. Oncogene. 2007;26:7773–7779

PII: S0046-8177(09)00294-9

doi: 10.1016/j.humpath.2009.08.008

Human Pathology
Volume 41, Issue 3 , Pages 358-365 , March 2010