Estrogen receptor alpha rapidly activates the IGF-1 receptor pathway.
Estrogen and insulin-like-growth factor 1 (IGF-1) are potent mitogenic stimuli that share important properties in the control of cellular proliferation. However, the coupling between the signaling cascades of estrogen receptors alpha and beta and the IGF-1 receptor (IGF-1R) is poorly understood. Therefore, we selectively transfected estrogen receptor alpha or beta in COS7 and HEK293 cells, which contain IGF-1R. In presence of estrogen receptor alpha but not beta, 17beta-estradiol (E2) rapidly induces phosphorylation of the IGF-1R and the extracellular signal-regulated kinases 1/2. Furthermore, upon stimulation with E2, estrogen receptor alpha but not beta bound rapidly to the IGF-1R in COS7 as well as L6 cells, which express all investigated receptors endogenously. Control experiments in the IGF-1R-deficient fibroblast cell line R(-) showed that after stimulation with E2 only estrogen receptor alpha bound to the transfected IGF-1R. Overexpression of dominant negative mitogen-activated protein kinases kinase inhibited this effect. Finally, estrogen receptor alpha but not beta is required to induce the activation of the estrogen receptor-responsive reporter ERE-LUC in IGF-1-stimulated cells. Taken together, these data demonstrate that ligand bound estrogen receptor alpha is required for rapid activation of the IGF-1R signaling cascade.
Kahlert
S
S
Medizinische Poliklinik and the Institut für Physiologie II, University of Bonn, 53111 Bonn, Germany.
Nuedling
S
S
van Eickels
M
M
Vetter
H
H
Meyer
R
R
Grohe
C
C
D000818:Animals; D019556:COS Cells; D002455:Cell Division; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D015398:Signal Transduction
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011960:Receptors, Estrogen; D017526:Receptor, IGF Type 1