An evaluation of the involvement of polyamines in modulating MCF-7 human breast cancer cell proliferation and progesterone receptor levels by estrogen and antiestrogen.
The present studies were undertaken to determine the importance of the polyamine biosynthetic pathway in cellular proliferation and hormone-regulated progesterone receptor synthesis in estrogen receptor-containing breast cancer cells. Treatment of MCF-7 cells with difluoromethylornithine (DFMO), the irreversible inhibitor of the enzyme ornithine decarboxylase (ODC), prevented estradiol-induced cell proliferation in a dose-dependent fashion. DFMO inhibition of estradiol-induced cell proliferation was completely recoverable by the addition of exogenous putrescine while putrescine alone did not stimulate proliferation of control cells. ODC activity was 4-fold greater in estrogen-treated cells and DFMO (5 mM) fully inhibited ODC activity. DFMO was able to suppress only slightly further the proliferation of antiestrogen (tamoxifen) treated cells and putrescine was able to recover this DFMO inhibition. In contrast to the suppressive effect of DFMO on cell proliferation, DFMO had no effect on the ability of estrogen to stimulate increased (4-fold elevated) levels of progesterone receptor. Hence, while ODC activity appears important for estrogen-induced cell proliferation, inhibition of the activity of this enzyme has no effect on the ability of estradiol to increase cellular progesterone receptor content.
D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D000518:Eflornithine / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000473:pathology*; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000502:physiology*; D011700:Putrescine / Q000494:pharmacology; D011980:Receptors, Progesterone / Q000096:biosynthesis*; D013629:Tamoxifen / Q000494:pharmacology
D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D011980:Receptors, Progesterone; D013629:Tamoxifen; D004958:Estradiol; D011700:Putrescine; D000518:Eflornithine