KLF4 ablation disrupts oral epithelial differentiation and increases squamous cell carcinomas upon chemical carcinogenesis

PAPARELLA M L; ABRIGO M.; COZZARIN M. E.; BAL DE KIER JOFFÉ, E; RAIMONDI ANA R.

Bariloche

Simposio; The Third South American Symposium in Signal Transduction and Molecular Medicine; 2015

IUBMB/SAIB/SAN/SAIC

Squamous cell carcinoma (SSC) of the head and neck is the sixth most common cancer and is rarely diagnosed in early stages. The early events in oral SCC carcinogenesis have been less studied and still poorly understood. In this regard, the transcription factor Krûppel-like factor 4 (Klf4) suppresses cell proliferation and promotes differentiation in stratified epithelia and helps to maintain homeostasis in epithelial cells. We have previously developed inducible mice carrying an oral-specific ablation of Klf4 (K14-CreERtam/Klf4flox/flox) which showed mild dysplastic lesions and abnormal differentiation in the tongue. With the aim to analyze if Klf4 cooperate in oral carcinogenesis we applied 4-nitroquinoline 1-oxide (4NQO), a chemical carcinogen, to this conditional Klf4 knockout mice line. 4NQO treated K14-CreERtam/Klf4flox/flox mice (KO 4NQO) showed a significant weight loss and developed more severe dysplastic lesions than control mice with 4NQO (p