Senescence evasion in melanoma progression: uncoupling of DNA-damage signaling from p53 activation and p21 expression.
Pigment Cell Melanoma Res
; 26(2): 226-35, 2013 Mar.
Article
en En
| MEDLINE
| ID: mdl-23253087
ABSTRACT
The best-established function of the melanoma-suppressor p16 is mediation of cell senescence, a permanent arrest following cell proliferation or certain stresses. The importance of p16 in melanoma suggests indolence of the other major senescence pathway through p53. Little or no p53 is expressed in senescent normal human melanocytes, but p16-deficient melanocytes can undergo p53-mediated senescence. As p16 expression occurs in nevi but falls with progression toward melanoma, we here investigated whether p53-dependent senescence occurs at some stage and, if not, what defects were detectable in this pathway, using immunohistochemistry. Phosphorylated checkpoint kinase 2 (CHEK2) can mediate DNA-damage signaling, and under some conditions senescence, by phosphorylating and activating p53. Remarkably, we detected no prevalent p53-mediated senescence in any of six classes of lesions. Two separate defects in p53 signaling appeared common in nevi, lack of p53 phosphorylation by activated CHEK2, and in melanomas, defective p21 upregulation by p53 even when phosphorylated.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Daño del ADN
/
Proteína p53 Supresora de Tumor
/
Senescencia Celular
/
Progresión de la Enfermedad
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Inhibidor p21 de las Quinasas Dependientes de la Ciclina
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Melanoma
Límite:
Humans
Idioma:
En
Revista:
Pigment Cell Melanoma Res
Asunto de la revista:
NEOPLASIAS
Año:
2013
Tipo del documento:
Article
País de afiliación:
Reino Unido