Deletion of 14-3-3σ sensitizes mice to DMBA/TPA-induced papillomatosis.
Oncotarget
; 7(30): 46862-46870, 2016 Jul 26.
Article
em En
| MEDLINE
| ID: mdl-27409835
ABSTRACT
The p53-inducible cell cycle regulator 14-3-3σ exhibits tumor suppressive functions and is highly expressed in differentiating layers of the epidermis and hair follicles. 14-3-3σ/SFN/stratifin is frequently silenced in human epithelial cancers, and experimental down-regulation of 14-3-3σ expression immortalizes primary human keratinocytes. In the repeated-epilation (ER) mouse model, a heterozygous nonsense mutation of 14-3-3σ causes repeated hair-loss, hyper-proliferative epidermis, and spontaneous development of papillomas and squamous cell carcinomas in aging mice. Therefore, loss of 14-3-3σ function might contribute to epithelial tumor development. Here, we generated mice with loxP sites surrounding the single 14-3-3σ exon which allowed Cre-mediated deletion of the gene. 14-3-3σ-deficient mice are viable, but demonstrate a permanently disheveled fur. However, histological analyses of the skin did not reveal obvious defects in the hair follicles or the epidermis. Deletion of 14-3-3σ did not enhance spontaneous epidermal tumor development, whereas it increased the frequency and size of DMBA/TPA-induced papillomas. In conclusion, 14-3-3σ is dispensable for normal epidermal homeostasis but critical for suppression of chemically-induced skin carcinogenesis. In addition, these results suggest that the ER mutation of 14-3-3σ is not equivalent to loss of 14-3-3σ, but may represent a gain-of-function variant, which does not reflect the organismal function of wild-type 14-3-3σ.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Papiloma
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Neoplasias Cutâneas
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Folículo Piloso
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Proteínas 14-3-3
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Epiderme
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Carcinogênese
Limite:
Animals
Idioma:
En
Revista:
Oncotarget
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Alemanha