Abstract
THE enzyme ornithine decarboxylase is the key regulator of the synthesis of polyamines1–3 which are essential for cell proliferation4,5. Expression of this enzyme is transiently increased upon stimulation by growth factors1–3, but becomes constitutively activated during cell transformation induced by carcinogens6,7, viruses8–10 or oncogenes11–14. To test whether ornithine decarboxylase could be a common mediator of transformation and oncogenic itself, we transfected NIH3T3 cells with expression vectors carrying the complementary DN A encoding human ornithine decarboxylase in sense and antisense orientations. The increased expression of the enzyme (50–100-times endogenous levels) induced not only cell transformation, but also anchorage-independent growth in soft agar and increased tyrosine phosphorylation of a protein of Mr130K. Expression of ornithine decarboxylase antisense RNA was associated with an epithelioid morphology and reduced cell proliferation. Moreover, blocking the endogenous enzyme using specific inhibitor or synthesizing antisense RNA prevented transformation of rat fibroblasts by temperature-sensitive v-src oncogene. Our results imply that the gene encoding ornithine decarboxylase is a proto-oncogene central for regulation of cell growth and transformation.
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References
Tabor, C. W. & Tabor, H. A. Rev. Biochem. 53, 749–790 (1984).
Pegg, A. E. Biochem. J. 234, 249–262 (1986).
Heby, O. & Persson, L. Trends biochem. Sci. 15, 153–158 (1990).
Steglich, C., Grens, A. & Scheffler, I. E. Somatic Cell molec. Gen. 11, 11–23 (1985).
Pohjanpelto, P., Hölttä, E. & Jänne, O. A. Molec. cell Biol. 5, 1385–1390 (1985).
Yuspa, S. H. et al. Nature 262, 402–404 (1976).
Gilmour, S. K., Verma, A. K., Madara, T. & O'Brien, T. G. Cancer Res. 47, 1221–1225 (1987).
Don, S. & Bachrach, U. Cancer Res. 35, 3618–3622 (1975).
Gazdar, A. F., Stull, H. B., Kilton, L. J. & Bachrach, U. Nature 262, 696–698 (1976).
Haddox, M. K., Magun, B. E. & Russell, D. H. Cancer Res. 40, 604–608 (1980).
Hölttä, E., Sistonen, L. & Alitalo, K. J. biol. Chem. 263, 4500–4507 (1988).
Chang, B. K., Libby, P. R., Bergeron, R. & Porter, C. W. Biochem. biophys. Res. Commun. 157, 264–270 (1988).
Sistonen, L., Hölttä, E., Mäkelä, T. P., Keski-Oja, J. & Alitalo, K. EMBO J. 8, 815–822 (1989).
Sistonen, L., Hölttä, E., Lehväslaiho, H., Lehtola, L. & Alitalo, K. J. Cell Biol. 109, 1911–1919 (1989).
Pohjanpelto, P., Virtanen, I. & Hölttä, E. Nature 293, 475–477 (1981).
Balasundaram, D., Tabor, C. W. & Tabor, H. Proc. natn. Acad. Sci. U.S.A. 88, 5872–5876 (1991).
Southern, P. J. & Berg, P. J. molec. appl. Genet. 1, 327–341 (1982).
Metcalf, B. W. et al. J. Am. chem. Soc. 100, 2551–2553 (1978).
Erikson, R. L., Purchio, A. F., Erikson, E., Collett, M. S. & Bruggs, J. S. Cell Biol. 87, 319–325 (1980).
Sefton, B. M., Hunter, T., Beemon, K. & Eckhart, W. Cell 20, 807–816 (1980).
Ellis, C., Moran, M., McCormick, F. & Pawson, T. Nature 343, 377–381 (1990).
Hibshoosh, H., Johnson, M. & Weinstein, I. B. Oncogene 6, 739–743 (1991).
Jänne, J., Hölttä, E., Kallio, A. & Käpyaho, K. Spec Top. endocrin. Metab. 5, 227–293 (1983).
Luk, G. D. & Baylin, S. B. New Engl. J. Med. 311, 80–83 (1984).
Pegg, A. E. Cancer Res. 48, 759–774 (1988).
Katz, A. & Kahana, C. EMBO J. 8, 1163–1167 (1989).
Tonin, P. N., Yeger, H., Stallings, R. L., Srinivasan, P. R. & Lewis, W. H. Oncogene 4, 1117–1121 (1989).
Seiler, N. et al. Cancer Res. 50, 5077–5083 (1990).
Hickock, N. J., Seppänen, P. J., Gunsalus, G. L. & Jänne, O. A. DNA 6, 179–187 (1987).
Mäkelä, T. P., Partanen, J., Schwab, M. & Alitalo, K. Gene 118, 293–294 (1992).
Gunning, P., Leavitt, J., Muscat, G., Ng, S-Y. & Kedes, L. Proc. natn. Acad. Sci U.S.A. 84, 4831–4835 (1987).
Jänne, O. A., Kontula, K. K., Isomaa, V. V. & Bardin, C. W. Ann. N.Y. Acad. Sci. 438, 72–84 (1984).
Sambrook, J., Fritsch, E. F. & Maniatis, T. Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Laboratory Press, New York, 1989).
Kamps, M. P. & Sefton, B. M. Oncogene 2, 305–315 (1988).
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Auvinen, M., Paasinen, A., Andersson, L. et al. Ornithine decarboxylase activity is critical for cell transformation. Nature 360, 355–358 (1992). https://doi.org/10.1038/360355a0
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DOI: https://doi.org/10.1038/360355a0
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