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). 17β-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. α-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.
This investigation was supported by the Medical Research Council of Canada.