Differential requirements of androgen receptor in luminal progenitors during prostate regeneration and tumor initiation

1 2 Differential requirements of androgen receptor in luminal progenitors during prostate 3 regeneration and tumor initiation 4 5 6

Dissecting cell-type-specific roles of androgen receptor in prostate homeostasis and regeneration through lineage tracing

Androgen signals through androgen receptor (AR) to influence prostate development and cancer. How stromal and epithelial AR regulate prostate homeostasis remains unclear. Using genetic lineage tracing, we systematically investigated the role of cell-autonomous AR in different prostate epithelial cell types. Here we show that AR is dispensable for basal cell maintenance, but is cell-autonomously...

Basal epithelial stem cells are efficient targets for prostate cancer initiation.

Prevailing theories suggest that luminal cells are the origin of prostate cancer because it is histologically defined by basal cell loss and malignant luminal cell expansion. We introduced a series of genetic alterations into prospectively identified populations of murine basal/stem and luminal cells in an in vivo prostate regeneration assay. Stromal induction of FGF signaling, increased expres...

Transcriptional regulation of Nkx3.1 in prostate luminal stem cell specification and cancer initiation via its 3′ genomic region

Nkx3.1, a transcription factor expressed in the prostate epithelium, is crucial for maintaining prostate cell fate and suppressing tumor initiation. Nkx3.1 is ubiquitously expressed in luminal cells of hormonally-intact prostate, but upon androgen deprivation, exclusively labels a type of luminal stem cells named castration-resistant Nkx3.1expressing cells (CARNs). During prostate cancer initia...

Histone 2B-GFP Label-Retaining Prostate Luminal Cells Possess Progenitor Cell Properties and Are Intrinsically Resistant to Castration

The existence of slow-cycling luminal cells in the prostate has been suggested, but their identity and functional properties remain unknown. Using a bigenic mouse model to earmark, isolate, and characterize the quiescent stem-like cells, we identify a label-retaining cell (LRC) population in the luminal cell layer as luminal progenitors. Molecular and biological characterizations show that thes...