title: Rapid estradiol/ERalpha signaling enhances aromatase enzymatic activity in breast cancer cells.
abstract: In situ estrogen production by aromatase conversion from androgens plays an important role in breast tumor promotion. Here, we show that 17beta-estradiol (E2) can rapidly enhance aromatase enzymatic activity through an increase of aromatase protein phosphorylation in breast cancer cell lines. In vivo labeling experiments and site-directed mutagenesis studies demonstrated that phosphorylation of the 361-tyrosine residue is crucial in the up-regulation of aromatase activity under E2 exposure. Our results demonstrated a direct involvement of nonreceptor tyrosine-kinase c-Src in E2-stimulated aromatase activity because inhibition of its signaling abrogated the up-regulatory effects induced by E2 on aromatase activity as well as phosphorylation of aromatase protein. In addition, from our data it emerges that aromatase is a target of cross talk between growth factor receptors and estrogen receptor alpha signaling. These findings show, for the first time, that tyrosine phosphorylation processes play a key role in the rapid changes induced by E2 in aromatase enzymatic activity, revealing the existence of a short nongenomic autocrine loop between E2 and aromatase in breast cancer cells.
authors: Department of Pharmaco-Biology, University of Calabria, Arcavacata di Rende (CS) 87030, Italy.
authors: Stefania
authors: S
authors: Catalano
authors: Ines
authors: I
authors: Barone
authors: Cinzia
authors: C
authors: Giordano
authors: Pietro
authors: P
authors: Rizza
authors: Hongyan
authors: H
authors: Qi
authors: Guowei
authors: G
authors: Gu
authors: Rocco
authors: R
authors: Malivindi
authors: Daniela
authors: D
authors: Bonofiglio
authors: Sebastiano
authors: S
authors: Andò
mesh_terms: D000595:Amino Acid Sequence; D001141:Aromatase / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D017978:Receptors, Growth Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D046912:Multiprotein Complexes; D017978:Receptors, Growth Factor; D019000:Phosphotyrosine; D004958:Estradiol; D001141:Aromatase; D066246:ErbB Receptors; D019061:src-Family Kinases