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

DARIO M. FERRI ; MICAELA N. STEDILE ; MARIELA VEGGETTI; MARÍA L. PAPARELLA ; EDITH KORDON ; ANA R. RAIMONDI

Buenos Aires

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

Oral squamous cell carcinoma is among the most prevalent cancersin the world characterized by high morbidity and few therapeuticoptions. RNA-binding proteins (RNA-BPs) that impact the stabilityof transcripts have a significant role in tumor progression. Tristetraprolin(TTP) is a RNA-BP that regulates multiple proinflammatorymediators which promote tumorigenesis. We have previouslydeveloped TTP conditional knock out mice specific for oral cavity(TTP KO). TTP KO mice developed moderate dysplastic lesionsin the tongue with deregulated expression of cytokeratins and proliferationmarkers. Here, to asses TTP role in oral carcinogenesiswe breed the TTP KO mice with a K-Ras knock in line (compoundmice: K14-CreERtam /TTP-/-/ K-rasG12D+/-). Tissues from these micewere used to study proliferation and differentiation by immunohistochemistry.The compound mice exhibited an oral phenotype aftera few weeks of tamoxifen induction leading to a significant reductionin survival time (compound mice: 40.25± 7.05 days; K-rasG12D+/-: 56.63± 1.99; TTP KO: 120±0.0. Kaplan?Meier survival curve,p