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Hormone‐activated nuclear receptors inhibit the stimulation of the JNK and ERK signalling pathways in endothelial cells
Author(s) -
González Marı́a Victoria,
González-Sancho José Manuel,
Caelles Carme,
Munoz Alberto,
Jiménez Benilde
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01257-0
Subject(s) - mapk/erk pathway , kinase , p38 mitogen activated protein kinases , medicine , endocrinology , glucocorticoid receptor , signal transduction , microbiology and biotechnology , retinoic acid , protein kinase a , glucocorticoid , chemistry , biology , cancer research , cell culture , genetics
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.