Oral-specific ablation of Klf4 disrupts epithelial terminal differentiation and increases premalignant lesions and carcinomas upon chemical carcinogenesis.
J Oral Pathol Med
; 44(10): 801-9, 2015 Nov.
Article
em En
| MEDLINE
| ID: mdl-25605610
ABSTRACT
BACKGROUND:
Squamous cell carcinoma (SSC) of the head and neck is the sixth most common cancer and is rarely diagnosed in early stages. The transcription factor KrÏppel-like factor 4 (Klf4) suppresses cell proliferation and promotes differentiation. Inducible mice carrying an oral-specific ablation of Klf4 (K14-CreER(tam) /Klf4(flox/flox) ) develop mild dysplastic lesions and abnormal differentiation in the tongue. Aiming to analyze whether Klf4 cooperate in oral chemical carcinogenesis,we applied 4-nitroquinoline 1-oxide (4NQO), a tobacco surrogate, to this conditional Klf4 knockout mice.METHODS:
K14-CreER(tam) /Klf4(flox/flox) and control mice were treated with 4NQO for 16 weeks and monitored until week 30. Histopathological samples were used for diagnostic purposes and immunofluorescence detection of epithelial differentiation markers.RESULTS:
4NQO-treated K14-CreER(tam) /Klf4(flox/flox) mice (Klf4KO 4NQO) showed a significant weight loss and developed more severe dysplastic lesions than control mice with 4NQO (P < 0.005). The Klf4KO 4NQO showed a tendency to higher incidence of oral SCC and a marked keratinization pattern in dysplasias, in situ carcinomas and SCC. Also, tongues derived from Klf4KO 4NQO mice exhibited reduced terminal differentiation as judged by cytokeratin 1 staining when compared with 4NQO-treated controls.CONCLUSIONS:
Klf4 ablation results in more severe dysplastic lesions in oral mucosa, with a tendency to higher incidence of SCC, after chemical carcinogenesis. We show here, in a context similar to the human carcinogenesis, that absence of Klf4 accelerates carcinogenesis and correlates with the absence of cytokeratin 1 expression. These results suggest a potential role for KLF4 as a tumor suppressor gene for the tongue epithelium.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Bucais
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Carcinoma de Células Escamosas
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Fatores de Transcrição Kruppel-Like
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Carcinogênese
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Neoplasias de Cabeça e Pescoço
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article