Epidermal growth factor receptor and tyrosine phosphorylation of estrogen receptor.
Activation of estrogen receptor-alpha (ERalpha) by growth factors in the absence of estrogen is a well-documented phenomenon. To study further this process of ligand-independent receptor activation, COS-7 cells without ER were transfected with both ER and epidermal growth factor receptor (EGFR). In the absence of estrogen, epidermal growth factor (EGF) stimulated rapid tyrosine phosphorylation of ER in transfected COS-7 cells. Similarly, in MCF-7 breast cancer cells that have natural expression of ER and EGFR, EGF promoted acute phosphorylation of serine and tyrosine residues in ER, and a direct interaction between ER and EGFR after treatment with EGF was found. In confirmation of a direct interaction between ER and EGFR, activation of affinity-purified EGFR tyrosine kinase in vitro stimulated the phosphorylation of recombinant ER. The cross-communication between EGFR and ER appears to promote significant stimulation of cell proliferation and a reduction in the apoptotic loss of those cells that express both receptor signaling pathways. However, COS-7 cells transfected with both ER and EGFR show minimal stimulation of classical estrogen response element (ERE)-dependent transcriptional activity after stimulation by EGF ligand. This suggests that the proliferative and antiapoptotic activity of EGF-induced ER activation may be dissociated from ERE-dependent transcriptional activity of the ER.
Márquez
D C
DC
UCLA School of Medicine, Department of Medicine, Division of Hematology-Oncology, Los Angeles, CA 90095-1678, USA.
Lee
J
J
Lin
T
T
Pietras
R J
RJ
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism; D019556:COS Cells; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000502:physiology*; D004967:Estrogens / Q000502:physiology; D005260:Female; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D011960:Receptors, Estrogen / Q000378:metabolism* / Q000502:physiology; D020218:Response Elements / Q000502:physiology; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism*
D004967:Estrogens; D011960:Receptors, Estrogen; D014443:Tyrosine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors