title: Lack of synergy between estrogen and progesterone on local IGF-I, IGFBP-3 and IGFBP-2 secretion by both hormone-dependent and hormone-independent breast cancer explants in vitro. Effect of tamoxifen and mifepristone (RU 486).
abstract: The aim of the present study was to investigate direct effects of estrogen (E2) or progesterone (P4) given separately vs. estrogen+progesterone on local IGF-I, IGFBP-3 and IGFBP-2 secretion. Explants obtained from estrogen receptor positive plus progesterone receptor positive (ER+/PR+) and hormone receptors negative (ER-/PR-) tumors were incubated with E2, P4 or both. Tamoxifen was added to E2-exposed cultures; mifepristone (RU 486) was added to P4, and both were given to E2+P4-supplemented cultures. In hormone-dependent and hormone-independent tissues, treatment with estrogen+progesterone increased IGF-I and IGFBP-2 secretion with concomitant decrease in IGFBP-3, in the same manner as E2 or P4 given alone. Tamoxifen decreased the E2- and E2+P4-stimulated IGF-I secretion by hormone-dependent breast cancer explants. RU 486 decreased the P4- and E2+P4-stimulated IGF-I secretion with parallel stimulation of IGFBP-3 secretion by ER+/PR+ explants. Estradiol and progesterone had a synergistic action on IGFBP-2 secretion by hormone-dependent breast cancer explants. In conclusion, the presented data suggest that there is no synergistic action of E2 and P4 in influencing IGF/IGFBPs ratio and, additionally, suggest a protective action of antiestrogen and antiprogestagen against excessive IGF-I secretion.
authors.affiliation: Department of Endocrinology and Fertility, Collegium Medicum, Jagiellonian University, Krakow, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Milewicz
authors.forename: Ewa Lucja
authors.initials: EL
authors.lastname: Gregoraszczuk
authors.forename: Krystyna
authors.initials: K
authors.lastname: Sztefko
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Augustowska
authors.forename: Józef
authors.initials: J
authors.lastname: Krzysiek
authors.forename: Janusz
authors.initials: J
authors.lastname: Ryś
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D004357:Drug Synergism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D015735:Mifepristone / Q000494:pharmacology*; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000503:physiopathology; D011374:Progesterone / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*; D046509:Tissue Culture Techniques
chemical_list: D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; D015735:Mifepristone; D011374:Progesterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I