Regulation of ribosomal protein S6 kinase in human mammary tumor cells: Effect of estrogen, growth factors and phorbol ester

Growth of human mammary tumor cells ZR-75-1 is stimulated by estradiol (E2), epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I). In these cells ribosomal protein S6 kinase is activated by EGF, IGF-I, insulin and phorbol 12-myristate 13-acetate (TPA) but not by E2. The human mammary tumor cell line MDA-MB 231, which is E2-receptor negative, has receptors for EGF, IGF-I and insulin but is unresponsive to these factors in terms of growth and S6 kinase activation. The role of protein kinase C (PKC) in the activation of S6 kinase by growth factors and TPA was investigated in ZR-75-1 cells. Down regulation of PKC activity by treatment with TPA for 48-h blocks the stimulation of S6 kinase by TPA but leaves the activation by EGF, IGF-I and insulin unaffected. In intact ZR-75-1 cells staurosporine blocks activation of S6 kinase by EGF and TPA, however with different IC50.