title: Estrogen-induced proliferation of urothelial cells is modulated by nerve growth factor.
abstract: Both nerve growth factor (NGF) and estrogen have been shown to stimulate proliferation of various cell types. Human urothelial cells (HUC) express the alpha- and beta-subtypes of the estrogen receptor (ER(alpha) and ER(beta)) as well as tyrosine kinase A (trkA), the high-affinity receptor for NGF. We investigated interactions between estrogen and NGF relative to cell proliferation using primary cultures of HUC. 17 beta-estradiol (E2) stimulated NGF synthesis by HUC, and E2 (50 nM), the ER(alpha) agonist 16 alpha-iodo-17 beta-estradiol (10 nM), or the ER(beta) agonist genistein (50 nM) each stimulated HUC proliferation, an effect that was abolished by the estrogen antagonist ICI-182,780 (100 nM). NGF (1-100 ng/ml) stimulated HUC proliferation, and this was abolished by NGF antiserum (0.1 microl/ml) or the trkA antagonist K252a (100 nM). HUC proliferation stimulated by E2 was also abolished by NGF antiserum or K252a. Finally, we observed that treatment of HUC with NGF (50 ng/ml) or E2 (50 nM) stimulated trkA phosphorylation, and this was abolished by K252a (100 nM) or NGF antiserum (0.1 microl/ml). These data indicate that the effects of ER activation on HUC proliferation at least partly involve activation of trkA by NGF.
authors: Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin 53706, USA.
authors: Jian
authors: J
authors: Teng
authors: Zun-Yi
authors: ZY
authors: Wang
authors: Dale E
authors: DE
authors: Bjorling
mesh_terms: D002227:Carbazoles / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D026121:Indole Alkaloids; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D020917:Receptor, trkA / Q000037:antagonists & inhibitors / Q000187:drug effects; D011960:Receptors, Estrogen / Q000819:agonists / Q000378:metabolism; D019459:Urothelium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D002227:Carbazoles; D004791:Enzyme Inhibitors; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D007106:Immune Sera; D026121:Indole Alkaloids; D011960:Receptors, Estrogen; D004958:Estradiol; D020932:Nerve Growth Factor; C049985:staurosporine aglycone; D019833:Genistein; D020917:Receptor, trkA