Development of low grade dysplasia in anal squamous epithelia upon specific activation of K-ras in a transgenic mouse system.

MARINA AYRE; GONZALO FERNANDEZ UGAZIO; ANA R RAIMONDI

Buenos Aires

Congreso; Reunion Anual de la Sociedad de Biociencias 2020; 2020

SAIC

Development of low grade dysplasia in anal squamous epithelia upon specific activation of K-ras in a transgenic mouse system.Marina Ayre, Gonzalo Fernandez Ugazio, Ana R RaimondiAnal SCC is a rare malignancy, accounting for only 4% of all cancers affecting the gastrointestinal tract. However, is one of the most common reported malignancy among men with HIV infection. ASCC treatment is associated with severe disease and treatment-related morbidity, therefore there is an urgent need to develop novel therapeutic approaches. The exact pathogenesis of ASCC remains unknown, the understanding of the molecular mechanisms involved have been hampered by the lack of animal models. Here, we took advantage of the driver line K14-CreERtam that we have previously characterized as a system that targets the basal layer of the squamous epithelia. Our aim was to characterize the expression of the driver system as well as the consequences of targeting activated ras to the anal epithelium. We breed the driver line with Rosa26 reporter animal line and with K-ras knock in mice. Tissues from these mice were used to study the phenotype and characterized by immunohistochemistry (IHC). The administration of tamoxifen to reporter mice resulted in the expression of EGFP in epithelia cells of the anal mucosa. K14-CreERtam/K-rasG12D/+ mice exhibited an anal phenotype 3 weeks after induction in contrast with a control group of K14-CreERtam (K14-CreERtam/K-rasG12D/+ 76 days (median survival). Kaplan?Meier survival curve, p