Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | International Journal of Gynecological Cancer |
| Vol/bind | 19 |
| Udgave nummer | 2 |
| Sider (fra-til) | 214-22 |
| Antal sider | 8 |
| ISSN | 1048-891X |
| DOI | |
| Status | Udgivet - 2009 |
Bibliografisk note
Keywords: Adenocarcinoma; Cell Line, Tumor; Cell Movement; Epidermal Growth Factor; Estradiol; Female; Humans; Ovarian Neoplasms; Receptors, Estrogen; Receptors, G-Protein-Coupled; Receptors, Urokinase Plasminogen Activator; Up-RegulationAdgang til dokumentet
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I: International Journal of Gynecological Cancer, Bind 19, Nr. 2, 2009, s. 214-22.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - Estradiol attenuates EGF-induced rapid uPAR mobilization and cell migration via the G-protein-coupled receptor 30 in ovarian cancer cells
AU - Henic, Emir
AU - Noskova, Vera
AU - Høyer-Hansen, Gunilla
AU - Hansson, Stefan
AU - Casslén, Bertil
N1 - Keywords: Adenocarcinoma; Cell Line, Tumor; Cell Movement; Epidermal Growth Factor; Estradiol; Female; Humans; Ovarian Neoplasms; Receptors, Estrogen; Receptors, G-Protein-Coupled; Receptors, Urokinase Plasminogen Activator; Up-Regulation
PY - 2009
Y1 - 2009
N2 - Epidermal growth factor (EGF) stimulates proliferation and migration in ovarian cancer cells, and high tumor expression of the EGF system correlates with poor prognosis. Epidermal growth factor upregulates urokinase plasminogen activator receptor (uPAR) on the cell surface via 3 distinct mechanisms: rapid mobilization of uPAR from detergent-resistant domains, increased mRNA, and decreased degradation. G-protein-coupled receptor 30 (GPR30) is a newly identified membrane estrogen receptor (ER).The objective of this study was to explore the effects of 17beta-estradiol (E(2)) on uPAR expression and cell migration in ovarian cancer cells and further to identify the ER involved.We used 7 ovarian cancer cell lines, cell migration assay, cellular binding of (125)I-uPA, cellular degradation of (125)I-uPA/PAI-1 complex, enzyme-linked immunosorbent assay for uPAR, solid-phase enzyme immunoassay for ERalpha, and quantitative polymerase chain reaction. Estradiol attenuates the stimulatory effect of EGF on cell migration and uPAR expression. Specifically, E(2) reduces the very rapid increase of detergent extractable uPAR, which occurs within minutes of EGF stimulation and probably represents mobilization of uPAR from detergent-resistant domains such as lipid rafts. Estradiol influenced neither the amount of uPAR mRNA nor the rate of uPAR degradation or solubilization. The nuclear ER antagonists ICI 182780 and tamoxifen, which are GPR30 agonists, as well as the specifically constructed GPR30 agonist G1, mimicked the effect of E(2) on uPAR expression and cell migration. OVCAR-3 cells express mRNA for GPR30.Estradiol attenuates EGF-induced mobilization of ligated uPAR from detergent-resistant domains and subsequent migration in ovarian cancer cells. The response to various ER ligands indicates that this effect is mediated via the membrane ER GPR30.
AB - Epidermal growth factor (EGF) stimulates proliferation and migration in ovarian cancer cells, and high tumor expression of the EGF system correlates with poor prognosis. Epidermal growth factor upregulates urokinase plasminogen activator receptor (uPAR) on the cell surface via 3 distinct mechanisms: rapid mobilization of uPAR from detergent-resistant domains, increased mRNA, and decreased degradation. G-protein-coupled receptor 30 (GPR30) is a newly identified membrane estrogen receptor (ER).The objective of this study was to explore the effects of 17beta-estradiol (E(2)) on uPAR expression and cell migration in ovarian cancer cells and further to identify the ER involved.We used 7 ovarian cancer cell lines, cell migration assay, cellular binding of (125)I-uPA, cellular degradation of (125)I-uPA/PAI-1 complex, enzyme-linked immunosorbent assay for uPAR, solid-phase enzyme immunoassay for ERalpha, and quantitative polymerase chain reaction. Estradiol attenuates the stimulatory effect of EGF on cell migration and uPAR expression. Specifically, E(2) reduces the very rapid increase of detergent extractable uPAR, which occurs within minutes of EGF stimulation and probably represents mobilization of uPAR from detergent-resistant domains such as lipid rafts. Estradiol influenced neither the amount of uPAR mRNA nor the rate of uPAR degradation or solubilization. The nuclear ER antagonists ICI 182780 and tamoxifen, which are GPR30 agonists, as well as the specifically constructed GPR30 agonist G1, mimicked the effect of E(2) on uPAR expression and cell migration. OVCAR-3 cells express mRNA for GPR30.Estradiol attenuates EGF-induced mobilization of ligated uPAR from detergent-resistant domains and subsequent migration in ovarian cancer cells. The response to various ER ligands indicates that this effect is mediated via the membrane ER GPR30.
U2 - 10.1111/IGC.0b013e31819bcb75
DO - 10.1111/IGC.0b013e31819bcb75
M3 - Journal article
C2 - 19395996
SN - 1048-891X
VL - 19
SP - 214
EP - 222
JO - International Journal of Gynecological Cancer
JF - International Journal of Gynecological Cancer
IS - 2
ER -