SOX2 is required independently in both stem and differentiated cells for pituitary tumorigenesis in <i>p27</i> -null mice
Verónica Moncho-Amor, Probir Chakravarty, Christophe Galichet, Ander Matheu, Robin Lovell‐Badge, Karine Rizzoti
Abstract
Significance Tumor development can depend on cell intrinsic dysfunction, but, in some cases, extrinsic factors are important drivers. Here, we established a genetically tractable model, demonstrating that the same gene is relevant both cell autonomously and noncell autonomously for tumorigenesis. Deletion of p27 , down-regulated in many tumors, predominantly leads to development of murine pituitary tumors. SOX2, transcriptionally derepressed in absence of P27, is important for tumorigenesis in this and other models, but little is known about its interaction. Using loss-of-function and lineage tracing approaches, we establish its regulatory interaction in vivo and show that SOX2 is required independently, both in endocrine and stem cells, to orchestrate tumorigenesis in absence of P27, establishing a powerful model to investigate mechanisms of tumor development.