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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
- 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.
- Subjects :
- Male
0301 basic medicine
Aging
Cell division
General Physics and Astronomy
Regenerative Medicine
Cell morphology
Transgenic
Androgen
Tissue Culture Techniques
Mice
Receptors
2.1 Biological and endogenous factors
Aetiology
Cancer
Principal Component Analysis
Multidisciplinary
biology
Prostate Cancer
Prostate
Cell biology
Organoids
Receptors, Androgen
Stem Cell Research - Nonembryonic - Non-Human
Stem cell
Urologic Diseases
Selective Estrogen Receptor Modulators
medicine.medical_specialty
Stromal cell
Genotype
medicine.drug_class
Science
1.1 Normal biological development and functioning
Mice, Transgenic
Article
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Underpinning research
Internal medicine
MD Multidisciplinary
medicine
Animals
PTEN
Regeneration (biology)
General Chemistry
Stem Cell Research
Androgen receptor
Tamoxifen
030104 developmental biology
Endocrinology
Gene Expression Regulation
biology.protein
Orchiectomy
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....13ae5cfc5f269df0a274cc340e8c89e0
- Full Text :
- https://doi.org/10.1038/ncomms14284