Increased Wingless (Wnt) signaling in pituitary progenitor/stem cells gives rise to pituitary tumors in mice and humans

摘要: Wingless (Wnt)/β-catenin signaling plays an essential role during normal development, is a critical regulator of stem cells, and has been associated with cancer in many tissues. Here we demonstrate that genetic expression degradation-resistant mutant form β-catenin early Rathke's pouch (RP) progenitors leads to pituitary hyperplasia severe disruption the pituitary-specific transcription factor 1-lineage differentiation resulting extreme growth retardation hypopituitarism. Mutant mice mostly die perinatally, but those survive weaning develop lethal tumors, which closely resemble human adamantinomatous craniopharyngioma, epithelial tumor mutations gene. The tumorigenic effect observed only when expressed undifferentiated RP progenitors, tumors do not committed or differentiated cells are targeted express this protein. Analysis affected pituitaries indicates significant increase total numbers progenitor/stem as well their proliferation potential. Our findings provide insights into Wnt pathway development causative for mutated progenitor genesis murine craniopharyngioma.