17beta-estradiol-induced activation of ERK1/2 through endogenous androgen receptor-estradiol receptor alpha-Src complex in human prostate cells.
We examined the effect of estrogens on mitogen-activated protein kinase (MAPK) in EPN cells, a line of epithelial cells derived from human normal prostate. 17beta-estradiol (E2) caused a rapid and transient activation of MAPK (ERK1/2) within 5 min. This effect was counteracted by the anti-estrogen ICI 182-780 and by MEK inhibitor PD098059. The activation of ERK1/2 through 17beta-estradiol triggered simultaneous association of endogenous androgen receptor, estrogen receptor alpha and Src. In addition, E2 stimulated the proliferation of EPN cells, suggesting that the formation of the ternary complex and the consequent activation of ERKs are implicated in the mechanism regulating proliferation of epithelial prostate cells.
Chieffi
Paolo
P
Dipartimento di Medicina Sperimentale, II Università di Napoli, Via Constantinopoli 16, I-80138 Naples, Italy. paolo.chieffi@unina2.it
Kisslinger
Annamaria
A
Sinisi
Antonio A
AA
Abbondanza
Ciro
C
Tramontano
Donatella
D
D015153:Blotting, Western; D002455:Cell Division; D002460:Cell Line; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011233:Precipitin Tests; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D011944:Receptors, Androgen / Q000378:metabolism*; D011959:Receptors, Estradiol / Q000378:metabolism*; D013997:Time Factors; D019061:src-Family Kinases / Q000378:metabolism*
D004791:Enzyme Inhibitors; D005419:Flavonoids; D020033:Protein Isoforms; D011944:Receptors, Androgen; D011959:Receptors, Estradiol; D004958:Estradiol; D019061:src-Family Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one