Notch signaling is required for normal prostatic epithelial cell proliferation and differentiation.

摘要: Notch pathway is crucial for stem/progenitor cell maintenance, growth and differentiation in a variety of tissues. Using transgenic ablation approach, we found our previous study that cells expressing Notch1 are prostate early development re-growth. Here, further define the role signaling regulating prostatic epithelial using biochemical genetic approaches ex vivo or systems. Treatment developing grown culture with inhibitors gamma-secretase/presenilin, which required cleavage activation, caused robust increase proliferation co-expressing cytokeratin 8 14, lack luminal/basal layer segregation dramatically reduced branching morphogenesis. conditional gene deletion mouse models, inactivation resulted profound alterations, including increased tufting, bridging enhanced proliferation. Cells within these lesions co-expressed both luminal basal markers, feature predifferentiation developmental stages. Microarray analysis revealed expression number networks was altered following prostate. Furthermore, its effector Hey-1 human adenocarcinomas were significantly down-regulated compared to normal control Taken together, data suggest critical prostate, deregulation this may facilitate tumorigenesis.