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

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

Authors :
Yueli Liu
Qing Xie
Joshua Stefanson
Corrigan Horton
Zhu A. Wang
Tao Cai
Source :
Nature Communications, Nature communications, vol 8, iss 1, Nature Communications, Vol 8, Iss 1, Pp 1-14 (2017)
Publication Year :
2017
Publisher :
Springer Science and Business Media LLC, 2017.

Abstract

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 required for the luminal differentiation of rare basal stem cells. In contrast, AR deletion in luminal cells alters cell morphology and induces transient over-proliferation, without affecting androgen-mediated luminal cell survival or regeneration. However, AR is selectively required for the maintenance of daughter cells produced by castration-resistant Nkx3.1-expressing luminal stem cells (CARNs). Notably, Pten loss can override AR-loss effects in both basal and luminal compartments to initiate tumours. Our data reveal distinct cell-type-specific roles of epithelial AR in orchestrating prostate homeostasis, and question the notion that epithelial AR serves as a tumour suppressor in early cancer initiation.<br />Androgen receptor is an important regulator of prostate development and cancer. In this study, the authors use genetic lineage tracing in mice to clarify the role of AR in different prostate epithelial cells.

Details

ISSN :
20411723
Volume :
8
Database :
OpenAIRE
Journal :
Nature Communications
Accession number :
edsair.doi.dedup.....13ae5cfc5f269df0a274cc340e8c89e0
Full Text :
https://doi.org/10.1038/ncomms14284