Expression of endothelial nitric oxide synthase is induced by estrogen with glycogen synthase 3beta phosphorylation in MCF-7 cells.
The endothelial nitric oxide synthase (eNOS) gene is induced by a variety of extracellular signals and NOS plays a key role in many physiological as well as pathological processes, including tumorgenesis. Some studies showed a positive correlation between the level of NOS protein and progression of malignancy in human breast cancer. In this study, we examined eNOS mRNA expression in human breast cancer cell lines. MCF-7 cells, which showed an estrogen receptor positive phenotype, were treated with estradiol or LiCl, a selective inhibitor of glycogen synthase kinase (GSK)-3beta. Both estradiol and LiCl enhanced the expression of eNOS mRNA with the phosphorylation of GSK-3beta, but not Akt. The induction was completely suppressed by the phosphatidylinositol 3-kinase (PI3-kinase) inhibitor LY294002, but not by PD98059, MEK-1 inhibitor nor rapamycin, p70S6 kinase inhibitor. We conclude that the estradiol-induced eNOS expression is modulated by PI3-kinase-dependent GSK-3beta pathway.
Nakatani
Kaname
K
Department of Laboratory Medicine, Mie University School of Medicine, Mie 514-8507, Japan. nakatani@clin.medic.mie-u.ac.jp
Horinouchi
Junichi
J
Yabu
Yasuyoshi
Y
Wada
Hideo
H
Nobori
Tsutomu
T
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D004967:Estrogens; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D048369:MAP Kinase Kinase 1; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D038762:Ribosomal Protein S6 Kinases, 70-kDa; C496314:NOS3 protein, human; C494918:AKT1 protein, human; C000605506:GSK3B protein, human; C482125:MAP2K1 protein, human