Role of polyamines in estradiol-induced growth of human breast cancer cells.
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). 17 beta-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. alpha-Difluoromethylornithine (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.
D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D002460:Cell Line; D000518:Eflornithine; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D009952:Ornithine / Q000031:analogs & derivatives / Q000494:pharmacology; D009955:Ornithine Decarboxylase / Q000032:analysis; D011073:Polyamines / Q000494:pharmacology / Q000502:physiology*
D011073:Polyamines; D004958:Estradiol; D009952:Ornithine; D009955:Ornithine Decarboxylase; D000518:Eflornithine