Glucocorticoids delay RAF-induced senescence promoted by EGR1.
Amino Acid Substitution
Cell Line
Cellular Senescence
/ drug effects
Cyclin-Dependent Kinase Inhibitor p15
Cyclin-Dependent Kinase Inhibitor p21
Early Growth Response Protein 1
/ genetics
Fibroblasts
/ metabolism
Glucocorticoids
/ pharmacology
Humans
MAP Kinase Signaling System
/ drug effects
Mutation, Missense
Proto-Oncogene Proteins B-raf
/ genetics
B-RAF-V600E
CDKN1A
CDKN2B
EGR1
Glucocorticoid
Oncogene-induced senescence
Journal
Journal of cell science
ISSN: 1477-9137
Titre abrégé: J Cell Sci
Pays: England
ID NLM: 0052457
Informations de publication
Date de publication:
22 08 2019
22 08 2019
Historique:
received:
13
02
2019
accepted:
22
07
2019
pubmed:
3
8
2019
medline:
9
7
2020
entrez:
3
8
2019
Statut:
epublish
Résumé
Expression of hyperactive RAF kinases, such as the oncogenic B-RAF-V600E mutant, in normal human cells triggers a proliferative arrest that blocks tumor formation. We discovered that glucocorticoids delayed the entry into senescence induced by B-RAF-V600E in human fibroblasts, and allowed senescence bypass when the cells were regularly passaged, but that they did not allow proliferation of cells that were already senescent. Transcriptome and siRNA analyses revealed that the EGR1 gene is one target of glucocorticoid action. Transcription of the
Identifiants
pubmed: 31371485
pii: jcs.230748
doi: 10.1242/jcs.230748
pii:
doi:
Substances chimiques
CDKN1A protein, human
0
CDKN2B protein, human
0
Cyclin-Dependent Kinase Inhibitor p15
0
Cyclin-Dependent Kinase Inhibitor p21
0
EGR1 protein, human
0
Early Growth Response Protein 1
0
Glucocorticoids
0
BRAF protein, human
EC 2.7.11.1
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2019. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interestsThe authors declare no competing or financial interests.