biostudies-literatureCalcagni AAssociazione Italiana per la Ricerca sul CancroMinistero della SaluteEuropean Research CouncilTelethonNINDS NIH HHSNational Institutes of HealthFondazione Antonio Carlo Monzinoe17047https://www.ebi.ac.uk/biostudies/studies/S-EPMC5036965biostudies-literatureUnknown5<i>TFE</i>-fusion renal cell carcinomas (<i>TFE</i>-fusion <i>RCCs</i>) are caused by chromosomal translocations that lead to overexpression of the <i>TFEB</i> and <i>TFE3</i> genes (Kauffman et al., 2014). The mechanisms leading to kidney tumor development remain uncharacterized and effective therapies are yet to be identified. Hence, the need to model these diseases in an experimental animal system (Kauffman et al., 2014). Here, we show that kidney-specific <i>TFEB</i> overexpression in transgenic mice, resulted in renal clear cells, multi-layered basement membranes, severe cystic pathology, and ultimately papillary carcinomas with hepatic metastases. These features closely recapitulate those observed in both <i>TFEB-</i> and <i>TFE3</i>-mediated human kidney tumors. Analysis of kidney seLifeModelling TFE renal cell carcinoma in mice reveals a critical role of WNT signaling.PMC5036965250154R01-NS078072TGM11CB6MCO 10.000R01 NS078072IG 2015 Id 1763914404IG 11904Leemans JCCalcagni ASettembre CSalvatore MMalouf GGZampelli NPece SNusco EBertalot GDi Fiore PPVerschuren EDe Cegli RConfalonieri Sde Heer EKors LBallabio APeters DJfalseModelling TFE renal cell carcinoma in mice reveals a critical role of WNT signaling.<i>TFE</i>-fusion renal cell carcinomas (<i>TFE</i>-fusion <i>RCCs</i>) are caused by chromosomal translocations that lead to overexpression of the <i>TFEB</i> and <i>TFE3</i> genes (Kauffman et al., 2014). The mechanisms leading to kidney tumor development remain uncharacterized and effective therapies are yet to be identified. Hence, the need to model these diseases in an experimental animal system (Kauffman et al., 2014). Here, we show that kidney-specific <i>TFEB</i> overexpression in transgenic mice, resulted in renal clear cells, multi-layered basement membranes, severe cystic pathology, and ultimately papillary carcinomas with hepatic metastases. These features closely recapitulate those observed in both <i>TFEB-</i> and <i>TFE3</i>-mediated human kidney tumors. Analysis of kidney s2016-01-01T00:00:00Z2016 Sep2026-04-17T23:24:04.607Z2019-03-27T02:25:09ZS-EPMC50369652766843110.7554/eLife.17047