Gene expression profiling of mouse prostate over-expressing the Notch1 intracellular domain.. Mus musculus

Molecular signaling that regulates differentiation, survival and proliferation of the prostate luminal epithelial cells has not been thoroughly understood. Herein, we show that increased canonical Notch1 activity suppresses terminal differentiation of prostate luminal epithelial cells but is insufficient to transform. Augmented Notch1 activity delays anoikis of luminal epithelial cells by augmenting NF-κB activity independent of Hes-1, stimulates luminal cell proliferation by potentiating the PI3K-AKT signaling, and rescues the capacities of a fraction of prostate luminal epithelial cells for unipotent differentiation in vivo and short-term self-renewal in vitro. Epithelial cell-autonomous AR signaling is dispensable for the Notch-mediated cellular survival and proliferation. This study reveals a previously unappreciated role of Notch in prostatic luminal epithelial cell differentiation, supports the presence of a lineage hierarchy within the prostate luminal epithelial cells, and implies a pro-metastatic function of Notch signaling during prostate cancer progression. Overall design: Two group comparison (WT and Mut)