Crosstalk between EGFR and extranuclear steroid receptors.
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.
Migliaccio
Antimo
A
Dipartimento di Patologia Generale, Facoltà di Medicina e Chirurgia, II Università di Napoli, Via L. De Crecchio, 7-80138 Naples, Italy.
Castoria
Gabriella
G
Di Domenico
Marina
M
Ciociola
Alessandra
A
Lombardi
Maria
M
De Falco
Antonietta
A
Nanayakkara
Merlin
M
Bottero
Daniela
D
De Stasio
Rosina
R
Varricchio
Lilian
L
Auricchio
Ferdinando
F
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
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