Roles of hormone replacement therapy and iron in proliferation of breast epithelial cells with different estrogen and progesterone receptor status.
Estrogen and iron play critical roles in a female body development and were investigated in the present study in relation to in vitro cell proliferation. Prempro, a hormone replacement therapy drug, and 17beta-estradiol (E2) were shown to increase cell proliferations in estrogen receptor positive (ER+) cells independent of progesterone receptor (PR) status. For example, increased cell proliferation was observed in ER+/PR+ human breast cancer MCF-7, its matching non-cancerous human breast epithelial MCF-12A, and ER+/PR+ murine mammary cancer MXT+ cells, but not in ER-/PR- MDA-MB-231, its matching non-cancerous MCF-10A, and MXT- (ER-/PR+) cells. By mimicking post-menopausal conditions of high estrogen in local breast tissue and increased iron levels due to cessation of menstrual periods, E2 and iron were shown to exert synergistic effects on proliferation of MCF-7 cells and significantly increased Ki67 and proliferating cell nuclear antigen. Western blotting of E2-treated ER+ but not ER- cells showed that E2 also increased transferrin receptor (TfR). Further studies are needed to assess the mitogenic effects of iron and estrogen in normal post-menopausal breast.
Dai
Jisen
J
Department of Environmental Medicine, New York University (NYU) Cancer Institute, NYU School of Medicine, PHL Room 802, 550 First Avenue, NY 10016, USA.
Jian
Jinlong
J
Bosland
Maarten
M
Frenkel
Krystyna
K
Bernhardt
Güenther
G
Huang
Xi
X
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D004338:Drug Combinations; D004847:Epithelial Cells / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007501:Iron / Q000494:pharmacology*; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000187:drug effects; D011980:Receptors, Progesterone / Q000187:drug effects
D004338:Drug Combinations; D004966:Estrogens, Conjugated (USP); C466383:Prempro; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D004958:Estradiol; D017258:Medroxyprogesterone Acetate; D007501:Iron