Estrogen receptor alpha rapidly activates the IGF-1 receptor pathway

Estrogen and insulin-like-growth factor 1 (IGF-1) are potent mitogenic stim uli that share important properties in the control of cellular proliferatio n. However, the coupling between the signaling cascades of estrogen recepto rs alpha and beta and the IGF-1 receptor (IGF-1R) is poorly understood. The refore, we selectively transfected estrogen receptor alpha or beta in COS7 and HEK293 cells, which contain IGF-1R. In presence of estrogen receptor al pha but not beta, 17 beta-estradiol (E2) rapidly induces phosphorylation of the IGF-IR and the extracellular signal-regulated kinases 1/2, Furthermore , upon stimulation with E2, estrogen receptor alpha but not beta bound rapi dly to the IGF-1R in COS7 as well as L6 cells, which express all investigat ed receptors endogenously, Control experiments in the IGF-1R-deficient fibr oblast cell line R- showed that after stimulation with E2 only estrogen rec eptor alpha bound to the transfected IGF-IR, Overexpression of dominant neg ative mitogen-activated protein kinases kinase inhibited this effect, Final ly, estrogen receptor alpha but not beta is required to induce the activati on of the estrogen receptor-responsive reporter ERE-LUC in IGF-1-stimulated cells. Taken together, these data demonstrate that ligand bound estrogen r eceptor alpha is required for rapid activation of the IGF-1R signaling casc ade.