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Role of Polyamines in Estradiol-induced Growth of Human Breast Cancer Cells¹

Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada R3E OW3

The present study explored the possible involvement of polyamines in estradiol-stimulated proliferation of human breast cancer cells using the estrogen-responsive subline of T-47D cells (clone 11). 17ß-Estradiol (10^-10 M) stimulated cell growth 2- to 4-fold. This estradiol-induced proliferation was associated with a peak (at 12–24 h) of activity of ornithine decarboxylase (ODC), the first and rate-limiting enzyme of polyamine biosynthesis. Estradiol-induced cell growth and ODC activity were observed only in the presence of 10% charcoal-treated fetal bovine serum, suggesting that serum factors are required for estrogen action. -Difluoromethylomithine (DFMO, 0.1 mM), a specific inhibitor of ODC, blocked the estradiol-induced cell proliferation and ODC activity. Putrescine (0.1 mM) rescued the inhibitory effect of DFMO on growth of steroid-treated cells. Putrescine alone was not stimulatory to cells, and in combinations with estradiol, it did not augment the effect of estradiol. In addition, DFMO abolished the estradiol-induced growth of several other hormone-responsive cell lines but did not affect the proliferation of unresponsive cells. Hormone-responsive cells exhibited differential sensitivity to DFMO; resistant cell lines (e.g., MCF-7) were found to possess higher endogeneous levels of ODC than sensitive cell lines (e.g., T-47D and ZR-75-1). Our findings indicate that polyamines are essential, although not sufficient, in estrogen stimulation of human breast cancer cells.

¹ This investigation was supported by the Medical Research Council of Canada.

² Scientist, Medical Research Council of Canada. To whom requests for reprints should be addressed.

Received 8/28/84. Revised 2/22/85. Accepted 3/12/85.

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