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Stromal AR inhibits prostate tumor progression by restraining secretory luminal epithelial cells
Stromal AR inhibits prostate tumor progression by restraining secretory luminal epithelial cells
- Source :
- Cell reports, vol 39, iss 8
- Publication Year :
- 2021
-
Abstract
- Androgen receptor (AR) is expressed in both the prostate epithelium and the prostate stroma and plays diverse roles in prostate physiology. Although low expression of stromal AR is clinically associated with advanced cancer stage and worse outcome, whether stromal AR inhibits or promotes prostate cancer progression remains controversial. Here, we specifically delete AR in smooth muscle cells of the adult mouse prostate under two tumorigenic conditions, namely, the Hi-Myc genetic model and the T+ E2 hormonal carcinogenesis model. Histology analyses show that stromal AR deletion exacerbates tumor progression phenotypes in both models. Furthermore, single-cell analyses of the tumor samples reveal that secretory luminal cells are the cell population particularly affected by stromal AR deletion, as they transition to a cellular state of potentiated PI3K-mTORC1 activities. Our results suggest that stromal AR normally inhibits prostate cancer progression by restraining secretory luminal cells and imply possible unintended negative effects of androgen deprivation therapy.
- Subjects :
- Cancer [CP]
Urologic Diseases
Male
Aging
Medical Physiology
Myc
PI3K
General Biochemistry, Genetics and Molecular Biology
Androgen
Mice
androgen receptor
Receptors
stroma
2.1 Biological and endogenous factors
Animals
mouse models
Aetiology
Cancer
Prostate Cancer
Prostate
Prostatic Neoplasms
Epithelial Cells
luminal cell
single cell
hormonal carcinogenesis
Receptors, Androgen
Biochemistry and Cell Biology
Stromal Cells
Subjects
Details
- ISSN :
- 22111247
- Volume :
- 39
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Cell reports
- Accession number :
- edsair.doi.dedup.....82ad56c4d4f58403926ba4db4ef70220