TRISTETRAPROLIN (TTP) ABLATION AND K-RAS ACTIVATION PROMOTE ABNORMAL ORAL EPITHELIUM PROLIFERATION AND DIFFERENTIATION

DARÍO FERRI; MICAELA STEDILE; VEGGETI M; PAPARELLA ML; KORDON E; ANA RAIMONDI

Congreso; Reunión Conjunta Sociedades Biociencias; 2017

Oral squamous cell carcinoma is among the most prevalent can- cers in the world characterized by high morbidity and few therapeu- tic options. RNA-binding proteins (RNA-BPs) that impact the stability of transcripts have a significant role in tumor progression. Tristet- raprolin (TTP) is a RNA-BP that regulates multiple proinflamma- tory mediators which promote tumorigenesis. We have previously developed TTP conditional knock out mice specific for oral cavity (TTP KO). TTP KO mice developed moderate dysplastic lesions in the tongue with deregulated expression of cytokeratins and pro- liferation markers. Here, to asses TTP role in oral carcinogenesis we breed the TTP KO mice with a K-Ras knock in line (compound mice: K14-CreERtam /TTP-/-/ K-rasG12D+/-). Tissues from these mice were used to study proliferation and differentiation by immunohis- tochemistry. The compound mice exhibited an oral phenotype af- ter a few weeks of tamoxifen induction leading to a significant re- duction in survival time (compound mice: 40.25± 7.05 days; K-ras G12D+/-: 56.63± 1.99; TTP KO: 120±0.0. Kaplan?Meier survival curve, p