This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Thomas, T. Articles by Kiang, D. T. Search for Related Content PubMed PubMed Citation Articles by Thomas, T. Articles by Kiang, D. T.

Regulation of Ornithine Decarboxylase Gene Expression in MCF-7 Breast Cancer Cells by Antiestrogens¹

Division of Toxicology, Department of Environmental and Community Medicine, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854 [T. T.]; Division of Oncology, Department of Medicine, University of Minnesota, Minneapolis, Minnesota [B. T., J. R. B., D. T. K.]; and the Center for Biomedical Research, The Population Council, New York [O. A. J.]

Ornithine decarboxylase (ODC) is an enzyme intimately related to cell growth regulation. The metabolic products of ODC, the polyamines, are known to play a vital role in the structure and function of biological macromolecules including nucleic acids and proteins. The activity of ODC is stimulated by estrogens in their target cells. In order to gain insight into the molecular mechanism of action of antiestrogens in human breast cancer, we studied the effect of tamoxifen and 4-hydroxytamoxifen on the concentration of ODC mRNA, ODC activity, and the polyamine levels in a hormone-responsive breast cancer cell line, MCF-7. ODC mRNA concentration was reduced to 40% of the controls after 6 h of treatment of the cells with 100 nM 4-hydroxytamoxifen, but tamoxifen had no significant effect on ODC mRNA after treating with even 1 µM concentration for 36 h. ODC activity was, however, reduced to 40 and 75% of the controls after 24 h of treatment with 4-hydroxytamoxifen and tamoxifen, respectively. There was a significant reduction in the concentration of putrescine to 63% of control in tamoxifen-treated cells, but spermidine and spermine levels were not affected. With 4-hydroxytamoxifen, putrescine, spermidine, and spermine levels were reduced to 41, 62, and 79% of the control, respectively. In addition, exogenous putrescine was able to reverse the growth inhibitory effects of 4-hydroxytamoxifen. Overall, these results indicate that ODC and polyamine levels in MCF-7 cells are controlled by antiestrogens, and that suppression of polyamine biosynthesis plays a critical role in the growth inhibitory effects of antiestrogens.

¹ This work was supported by the National Cancer Institute R23-CA-42439 (T. T.), Environmental and Occupational Health Science Institute, Piscataway, NJ (T. T.), UMDNJ Foundation (T. T.), the Minnesota Medical Foundation (D. T. K.), and by the American Cancer Society PDT 323 (D. T. K.).

² To whom requests for reprints should be addressed, at Department of Environmental and Community Medicine, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854.

Received 11/16/88. Revised 4/ 5/89. Revised 7/17/89. Accepted 8/ 4/89.

This article has been cited by other articles:

				V. Vijayanathan, S. Venkiteswaran, S. K. Nair, A. Verma, T.J. Thomas, B. T. Zhu, and T. Thomas Physiologic levels of 2-methoxyestradiol interfere with nongenomic signaling of 17beta-estradiol in human breast cancer cells. Clin. Cancer Res., April 1, 2006; 12(7 Pt 1): 2038 - 2048. [Abstract] [Full Text] [PDF]

				J. S Lewis, T J Thomas, R. G Pestell, C. Albanese, M. A Gallo, and T. Thomas Differential effects of 16{alpha}-hydroxyestrone and 2-methoxyestradiol on cyclin D1 involving the transcription factor ATF-2 in MCF-7 breast cancer cells J. Mol. Endocrinol., February 1, 2005; 34(1): 91 - 105. [Abstract] [Full Text] [PDF]

				M J Campbell, J V Woodside, J Secker-Walker, A Titcomb, and A J C Leathem IGF status is altered by tamoxifen in patients with breast cancer Mol. Pathol., October 1, 2001; 54(5): 307 - 310. [Abstract] [Full Text] [PDF]

				F. Canizares, J. Salinas, M. d. las Heras, J. Diaz, I. Tovar, P. Martinez, and R. Penafiel Prognostic Value of Ornithine Decarboxylase and Polyamines in Human Breast Cancer: Correlation with Clinicopathologic Parameters Clin. Cancer Res., August 1, 1999; 5(8): 2035 - 2041. [Abstract] [Full Text] [PDF]

				M. Lessard, C. Zhao, S. M. Singh, and R. Poulin Hormonal and Feedback Regulation of Putrescine and Spermidine Transport in Human Breast Cancer Cells J. Biol. Chem., January 27, 1995; 270(4): 1685 - 1694. [Abstract] [Full Text] [PDF]