title: Crosstalk between EGFR and extranuclear steroid receptors.
abstract: Epidermal growth factor (EGF) stimulates DNA synthesis and cytoskeletal rearrangement in human breast cancer (MCF-7) and human prostate cancer (LNCaP) cells. Both effects are inhibited by estrogen (ICI 182,780) and androgen (Casodex) antagonists. This supports the view that crosstalk exists between EGF and estradiol (ER) and androgen (AR) receptors and suggests that these receptors are directly involved in the EGF action. Our recent work shows that EGF stimulates ER phosphorylation on tyrosine and promotes the association of a complex between EGFR, AR/ER, and the kinase Src. The complex assembly triggers Src activity, epidermal growth factor receptor (EGFR) phosphorylation on tyrosine, and the EGF-dependent signaling pathway activation. In these cells, the AR/ER/Src complex is required for the EGF action, as the growth factor effects are abolished upon receptor silencing by specific SiRNAs and steroid antagonists or Src inhibition by the kinase inhibitor PP2.
authors.affiliation: Dipartimento di Patologia Generale, Facoltà di Medicina e Chirurgia, II Università di Napoli, Via L. De Crecchio, 7-80138 Naples, Italy.
authors.forename: Antimo
authors.initials: A
authors.lastname: Migliaccio
authors.forename: Gabriella
authors.initials: G
authors.lastname: Castoria
authors.forename: Marina
authors.initials: M
authors.lastname: Di Domenico
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ciociola
authors.forename: Maria
authors.initials: M
authors.lastname: Lombardi
authors.forename: Antonietta
authors.initials: A
authors.lastname: De Falco
authors.forename: Merlin
authors.initials: M
authors.lastname: Nanayakkara
authors.forename: Daniela
authors.initials: D
authors.lastname: Bottero
authors.forename: Rosina
authors.initials: R
authors.lastname: De Stasio
authors.forename: Lilian
authors.initials: L
authors.lastname: Varricchio
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Auricchio
mesh_terms: D059002:Androgen Receptor Antagonists; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000819:agonists / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D008297:Male; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000378:metabolism*; D020239:Receptor Cross-Talk; D011944:Receptors, Androgen / Q000378:metabolism*; D011987:Receptors, Steroid / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism; D015854:Up-Regulation; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D059002:Androgen Receptor Antagonists; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D011944:Receptors, Androgen; D011987:Receptors, Steroid; D000077267:Fulvestrant; D014443:Tyrosine; D004958:Estradiol; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D019061:src-Family Kinases