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Differential cross-talk of estrogen and growth factor receptors in two human mammary tumor cell lines

Item Type:Article
Title:Differential cross-talk of estrogen and growth factor receptors in two human mammary tumor cell lines
Creators Name:Lichtner, R.B., Parczyk, K., Birchmeier, W. and Schneider, M.R.
Abstract:Cultured human mammary MCF7 and T47D tumor cell lines were used to test the interference of the partial antiestrogen 4'-hydroxytamoxifen (4-OH-TAM) and the pure antiestrogen ZM 182780 with growth factor (IGF-I, heregulin) signaling pathways. Growth of both cell lines was stimulated by IGF-I (20 ng/ml) or heregulin (3 nM). ZM 182780 effectively blocked growth factor induced as well as basal proliferation of MCF7 cells while the compound was ineffective in interfering with growth factor mitogenic activity in T47D cells. On both cell lines the IGF-I or heregulin- induced proliferation was enhanced further by 4-OH-TAM. This synergism could be inhibited dose-dependently by ZM 182780. When cells were grown in the presence of estradiol plus growth factors, the antiestrogenic potencies of both compounds and the efficacy of ZM 182780 were unaffected, while the efficacy of 4-OH-TAM was reduced. Our data show cell type specific cross-talk between the receptor for estrogen and that for IGF-I or heregulin, which is different in MCF7 and T47D cells, respectively. In MCF7 cells with demonstrable cross-talk, a clear superiority exists for a pure antiestrogen over a partial agonist in interfering with growth factor mitogenic activity.
Keywords:Breast Neoplasms, Cell Division, Cultured Tumor Cells, Estradiol, Estrogen Receptor Modulators, Estrogen Receptors, Insulin-Like Growth Factor I, Neuregulin-1, Signal Transduction, Tamoxifen
Source:Journal of Steroid Biochemistry and Molecular Biology
ISSN:0960-0760
Publisher:Pergamon Press
Volume:71
Number:5-6
Page Range:181-189
Date:31 December 1999
Official Publication:https://doi.org/10.1016/S0960-0760(99)00136-3
PubMed:View item in PubMed

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