American Association for Cancer Research
00085472can141218-sup-130432_2_supp_2585847_n9gpn1.xlsx (37.14 kB)

Supp Table S5 from In Vivo Disruption of an Rb–E2F–Ezh2 Signaling Loop Causes Bladder Cancer

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posted on 2023-03-30, 22:47 authored by Mirentxu Santos, Mónica Martínez-Fernández, Marta Dueñas, Ramón García-Escudero, Begoña Alfaya, Felipe Villacampa, Cristina Saiz-Ladera, Clotilde Costa, Marta Oteo, José Duarte, Victor Martínez, Ma José Gómez-Rodriguez, Ma Luisa Martín, Manoli Fernández, Patrick Viatour, Miguel A. Morcillo, Julien Sage, Daniel Castellano, Jose L. Rodriguez-Peralto, Federico de la Rosa, Jesús M Paramio

Supp Table S5. Transcription factor analyzed by Chip Enrichment analysis of the downregulated genes in mouse bladder tumors.



Bladder cancer is a highly prevalent human disease in which retinoblastoma (Rb) pathway inactivation and epigenetic alterations are common events. However, the connection between these two processes is still poorly understood. Here, we show that the in vivo inactivation of all Rb family genes in the mouse urothelium is sufficient to initiate bladder cancer development. The characterization of the mouse tumors revealed multiple molecular features of human bladder cancer, including the activation of E2F transcription factor and subsequent Ezh2 expression and the activation of several signaling pathways previously identified as highly relevant in urothelial tumors. These mice represent a genetically defined model for human high-grade superficial bladder cancer. Whole transcriptional characterizations of mouse and human bladder tumors revealed a significant overlap and confirmed the predominant role for Ezh2 in the downregulation of gene expression programs. Importantly, the increased tumor recurrence and progression in human patients with superficial bladder cancer is associated with increased E2F and Ezh2 expression and Ezh2-mediated gene expression repression. Collectively, our studies provide a genetically defined model for human high-grade superficial bladder cancer and demonstrate the existence of an Rb–E2F–Ezh2 axis in bladder whose disruption can promote tumor development. Cancer Res; 74(22); 6565–77. ©2014 AACR.