Hormone-activated nuclear receptors inhibit the stimulation of the JNK and ERK signalling pathways in endothelial cells.
Glucocorticoid hormones, retinoids, and vitamin D3 display anti-angiogenic activity in tumor-bearing animals. However, despite their in vivo effect on the tumor vasculature little is known about their mechanism of action. Here we show that the synthetic glucocorticoid dexamethasone (Dex) and retinoic acid (RA) inhibit the activation of c-Jun N-terminal kinase (JNK) and extracellular-regulated kinase (ERK) signalling pathways by the pro-angiogenic agents tumor necrosis factor and vascular endothelial growth factor in endothelial cells. In contrast, Dex and RA failed to inhibit the activation of the p38 mitogen-activated protein kinase cascade. As a number of pro-angiogenic factors activate AP-1 transcription factor via the JNK and ERK pathways, our results suggest that the antagonism with AP-1 may underlie at least partially the anti-angiogenic effect of glucocorticoids and retinoids.
González
M V
MV
Instituto de Investigaciones Biomédicas 'Alberto Sols', Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Arturo Duperier 4, E-28029, Madrid, Spain.
González-Sancho
J M
JM
Caelles
C
C
Munoz
A
A
Jiménez
B
B
D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D004789:Enzyme Activation; D005938:Glucocorticoids / Q000494:pharmacology; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D008222:Lymphokines / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000096:biosynthesis / Q000378:metabolism*; D015398:Signal Transduction; D014212:Tretinoin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D048051:p38 Mitogen-Activated Protein Kinases
D016228:Endothelial Growth Factors; D005938:Glucocorticoids; D006728:Hormones; D008222:Lymphokines; D018160:Receptors, Cytoplasmic and Nuclear; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014212:Tretinoin; D003907:Dexamethasone; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases