Loss of tristetraprolin (TTP) and K-ras activation promote development of premalignant oral lesions in a conditional transgenic system.

FERRI D; ANA R RAIMONDI; PAPARELLA M L; COSO O A

Bariloche, Argentina

Simposio; The Fourth South American Symposium in Signal Transduction and Molecular Medicine; 2018

SISTAM

Oral squamous cell carcinoma is the sixth most common cancer worldwide with a survival rate below 50% after diagnosis. Limited survival of patients is likely due to most of them presenting with advanced disease stages and no response to available chemotherapy. RNA-binding proteins (RNA-BPs) that impact the stability of transcripts play a key role in disease pathogenesis. Tristetraprolin (TTP) is a RNA-BP that regulates proinflammatory 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. Here, to asses TTP role in oral carcinogenesis we breed a K-Ras G12D+/- knock in line (K-Ras) with the TTP KO mice (Ho-compound mice: K14-CreERtam/TTP-/-/K-rasG12D+/-). Compound mice heterozygous for TTP were also studied (Het-compound mice). Compound mice exhibited an oral phenotype after tamoxifen induction leading to a significant reduction in survival time (Ho-compound mice: 31±2.9 days; Het-compound mice: 53.5±6.6; K-ras: 56.6± 1.9; TTP KO: 120±0.0. Kaplan?Meier survival curve, p