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Structure, Amplification and Methylation of Ornithine Decarboxylase Genes in Human Malignant Cells

  • Juhani Jänne
  • Leena Alhonen
  • Ari Hirvonen
  • Jarmo Wahlfors
  • Riitta Sinervirta
  • Terho Eloranta
  • Erkki Hölttä
  • Arja Kallio
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 250)

Abstract

Ornithine decarboxylase (ODC; EC 4.1.1.17) belongs to those enzymes which in response to metabolic stress are overproduced by exposed tumor cells. Mouse tumor cells easily acquire resistance to α-difluoromethylornithine (DFMO), a mechanism based irreversible inhibitor of ODC by overproducing the enzyme through amplification of transcriptionally active genes (1, 2, 3) or as a results of more efficient transcription or translation at normal gene copy number (4, 5).

Keywords

Chronic Lymphocytic Leukemia Chinese Hamster Ovary Cell Polycythemia Vera Ornithine Decarboxylase Arginase Activity 
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.

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References

  1. 1.
    McConlogue, L., Gupta, M., Wu, L., and Coffino, P., 1984. Molecular cloning and expression of the mouse ornithine decarboxylase gene. Proc. Natl. Acad. USA 81: 540.CrossRefGoogle Scholar
  2. 2.
    Kahana, C., and Nathans, D., 1984. Isolation of cloned cDNA encoding mammalian ornithine decarboxylase. Proc. Natl. Acad. Sci. USA 81: 3645.PubMedCrossRefGoogle Scholar
  3. 3.
    Alhonen-Hongisto, L., Kallio, A., Sinervirta, R., Seppänen, P., Kontula, K.K., Jänne, O.A., and Jänne, J., 1985. Difluoromethylornithine-induced amplification of ornithine decarboxylase genes in Ehrlich ascites carcinoma cells. Biochem. Biophys. Res. Commun. 126: 734.PubMedCrossRefGoogle Scholar
  4. 4.
    Alhonen-Hongisto, L., Sinervirta, R., Jänne, O.A., and Jänne, J., 1985. Gene expression of ornithine decarboxylase in L1210 leukaemia cells exposed to DL-2-difluoromethylornithine in the presence of cadaverine. Biochem. J. 232: 605.PubMedGoogle Scholar
  5. 5.
    McConlogue, L., Dana, S.L. and Coffino, P., 1986. Multiple mechanisms are responsible for altered expression of ornithine decarboxylase in overproducing variant cells. Mol. Cell. Biol. 6: 2865.PubMedGoogle Scholar
  6. 6.
    Leinonen, P., Alhonen-Hongisto, L., Laine, R., Jänne, O.A., and Jänne, J., 1987. Human myeloma cells acquire resistance to difluoromethylornithine by amplification of ornithine decarboxylase gene. Biochem. J. 242: 199.PubMedGoogle Scholar
  7. 7.
    Alhonen-Hongisto, L., Leinonen, P., Laine, R., and Jänne, J., 1987. Human myeloma cells acquire resistance to difluoromethylornithine without overproducing ornithine decarboxylase. Biochem. Biophys. Res. Commun. 144: 132.PubMedCrossRefGoogle Scholar
  8. 8.
    Winqvist, R., Mäkelä, T.P., Seppänen, P., Jänne, O.A., Alhonen-Hongisto, L., Jänne, J., Grzeschik, K.-H., and Alitalo, K., 1986. Human ornithine decarboxylase sequences map to chromosome regions 2pter p23 and 7cen qter but are not amplified with the NMYC oncogene. Cytogenet. Cell Genet. 42: 133.PubMedCrossRefGoogle Scholar
  9. 9.
    Alhonen-Hongisto, L., Leinonen, P., Sinervirta, R., Laine, R., Winqvist, R., Alitalo, K., Jänne, O.A., and Jänne, J., 1987. Mouse and human ornithine decarboxylase genes. Biochem. J. 242: 205.PubMedGoogle Scholar
  10. 10.
    Fukunaga, R., Matsuyama, M., Okamura, H., Nagata, K., Nagata, S., and Sokawa, Y., 1986. Undermethylation of interferon-gamma gene in human T cell lines and normal T lymphocytes. Nucleic Acids Res. 14: 4421.PubMedCrossRefGoogle Scholar
  11. 11.
    Doerfler, W., 1983. DNA methylation and gene activity. Ann. Rev. Biochem. 52: 93.PubMedCrossRefGoogle Scholar
  12. 12.
    Leinonen, P., Alhonen-Hongisto, L., Laine, R., Jänne, O.A., and Jänne, J., 1987. Chronic exposure to dexamethasone induces hypomethylation of ornithine decarboxylase genes in a human myeloma cell line. FEBS Lett. 215: 68.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Juhani Jänne
    • 1
  • Leena Alhonen
    • 1
  • Ari Hirvonen
    • 1
  • Jarmo Wahlfors
    • 1
  • Riitta Sinervirta
    • 1
  • Terho Eloranta
    • 1
  • Erkki Hölttä
    • 2
  • Arja Kallio
    • 3
  1. 1.Department of BiochemistryUniversity of KuopioKuopioFinland
  2. 2.Department of PathologyUniversity of HelsinkiFinland
  3. 3.Orion Genetic Engineering LaboratoryHelsinkiFinland

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