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Variations in amplification and expression of the ornithine decarboxylase gene in human breast cancer cells

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Abstract

The polyamine biosynthetic pathway plays a critical role in the growth of human breast cancer cells. Ornithine decarboxylase (ODC) is a key enzyme in polyamine biosynthesis. To understand the regulation of ODC activity and polyamine accumulation in breast cancer cells, we studied amplification and expression of the ODC gene in four breast cancer cell lines. ODC gene dosage was analyzed by Southern blot hybridization and was 4- to 12-fold higher in T-47D, MDA-MB-231, and BT-20 cell lines than in the MCF-7 cell line. ODC mRNA level was 2- to 3-fold higher in BT-20 and MDA-MB-231 cell lines than in the other two lines. We also measured ODC activity and polyamine concentration in these cell lines, and determined their sensitivity to an ODC inhibitor, difluoromethylornithine (DFMO). BT-20 cells showed significantly higher ODC activity and polyamine concentrations than the other three cell lines. BT-20 cells were resistant to the growth inhibitory effect of DFMO even at 4 mM concentration, whereas the proliferation of MCF-7, T47D, and MDA-MB-231 cells was inhibited by this drug. These results suggest that different transcriptional and post-transcriptional mechanisms control the regulation of ODC gene expression in breast cancer cell lines.

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Authors and Affiliations

  1. Division of Toxicology, Department of Environmental and Community Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, 08854, Piscataway, NJ

    Thresia Thomas

  2. Clinical Research Center and Division of Rheumatology, Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, 08854, Piscataway, NJ

    T. J. Thomas

  3. Division of Oncology, Department of Medicine, University of Minnosota, 55455, Minneapolis, MN

    David T. Kiang

  4. The Population Council, Rockefeller University [O.A.J.], New York

    Olli A. Jänne

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  1. Thresia Thomas
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  3. Olli A. Jänne
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  4. T. J. Thomas
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Thomas, T., Kiang, D.T., Jänne, O.A. et al. Variations in amplification and expression of the ornithine decarboxylase gene in human breast cancer cells. Breast Cancer Res Tr 19, 257–267 (1991). https://doi.org/10.1007/BF01961162

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