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

Cultured human mammary MCF7 and T47D tumor cell lines were used to test the interference of the partial antiestrogen 4'-hydroxytamoxifen (4-OH-TAM) an d the pure antiestrogen ZM 182780 with growth factor (IGF-I, heregulin) sig naling pathways. Growth of both cell lines was stimulated by IGF-I (20 ng/m l) or heregulin (3 nM). ZM 182780 effectively blocked growth factor induced as well as basal proliferation of MCF7 cells while the compound was ineffe ctive in interfering with growth factor mitogenic activity in T47D cells. O n both cell lines the IGF-I or heregulin- induced proliferation was enhance d further by 4-OH-TAM. This synergism could be inhibited dose-dependently b y ZM 182780. When cells were grown in the presence of estradiol plus growth factors, the antiestrogenic potencies of both compounds and the efficacy o f ZM 182780 were unaffected, while the efficacy of COH-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 superior ity exists for a pure antiestrogen over a partial agonist in interfering wi th growth factor mitogenic activity. (C) 2000 Elsevier Science Ltd. All rig hts reserved.