Skin epidermis lacking the c-Myc gene is resistant to Ras-driven tumorigenesis but can reacquire sensitivity upon additional loss of the p21Cip1 gene

Détails

ID Serval
serval:BIB_D9FA9696AFCD
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Skin epidermis lacking the c-Myc gene is resistant to Ras-driven tumorigenesis but can reacquire sensitivity upon additional loss of the p21Cip1 gene
Périodique
Genes & Development
Auteur(s)
Oskarsson T., Essers M. A., Dubois N., Offner S., Dubey C., Roger C., Metzger D., Chambon P., Hummler E., Beard P., Trumpp A.
ISSN
0890-9369 (Print)
Statut éditorial
Publié
Date de publication
08/2006
Volume
20
Numéro
15
Pages
2024-29
Notes
Journal Article Research Support, Non-U.S. Gov't --- Old month value: Aug 1
Résumé
The target gene(s) required for Myc-mediated tumorigenesis are still elusive. Here we show that while endogenous c-Myc is surprisingly dispensable for skin homeostasis and TPA-induced hyperplasia, c-Myc-deficient epidermis is resistant to Ras-mediated DMBA/TPAinduced tumorigenesis. This is mechanistically linked to p21(Cip1), which is induced in tumors by the activated Ras-ERK pathway but repressed by c-Myc. Acute elimination of c-Myc in established tumors leads to the up-regulation of p21(Cip1), and epidermis lacking both p21(Cip1) and c-Myc reacquires normal sensitivity to DMBA/TPA-induced tumorigenesis. This identifies c-Myc-mediated repression of p21(Cip1) as a key step for Ras-driven epidermal tumorigenesis.
Mots-clé
9,10-Dimethyl-1,2-benzanthracene/toxicity Animals *Cell Transformation, Neoplastic Cyclin-Dependent Kinase Inhibitor p21/*metabolism Epidermis/*metabolism Female Gene Expression Regulation, Neoplastic Genes, ras/*physiology Male Mice Mitogen-Activated Protein Kinase 1/metabolism Mitogen-Activated Protein Kinase 3/metabolism Proto-Oncogene Proteins c-myc/genetics/*physiology *Signal Transduction Skin Neoplasms/chemically induced/*pathology Tetradecanoylphorbol Acetate/toxicity Up-Regulation
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 13:42
Dernière modification de la notice
20/08/2019 16:59
Données d'usage