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Epidermal growth factor receptor and tyrosine phosphorylation of estrogen receptor

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Abstract

Activation of estrogen receptor-α (ERα) 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.

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  1. Department of Medicine, Division of Hematology-Oncology, UCLA School of Medicine, 10833 Le Conte Avenue, 11-934 Factor Building, 90095-1678, Los Angeles, CA

    Diana C. Márquez, Julie Lee, Theodore Lin &  Richard J. Pietras

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  1. Diana C. Márquez
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Márquez, D.C., Lee, J., Lin, T. et al. Epidermal growth factor receptor and tyrosine phosphorylation of estrogen receptor. Endocr 16, 73–81 (2001). https://doi.org/10.1385/ENDO:16:2:073

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