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Role of Runx2 in prostate development and stem cell function
Author(s) -
Li Yan,
Ge Chunxi,
Franceschi Renny T.
Publication year - 2021
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.24099
Subject(s) - stem cell , prostate , runx2 , biology , prostate cancer , cancer stem cell , cancer research , transcription factor , microbiology and biotechnology , cancer , biochemistry , gene , genetics
Background RUNX2, a critical transcription factor in bone development, is also expressed in prostate and breast where it has been linked to cancer progression and cancer stem cells. However, its role in normal prostate biology has not been previously examined. Methods Selective growth of murine prostate epithelium under non‐adherent conditions was used to enrich for stem cells. Expression of runt domain transcription factors, stem cell and prostate marker messenger RNAs (mRNAs) was determined by quantitative reverse transcription polymerase chain reaction. Effects of Runx2 loss and gain‐of‐function on prostate epithelial cells were assessed using cells isolated from Runx2 loxp/loxp mice transduced with Adeno‐Cre or by Adeno‐Runx2 transduction of wild type cells. Cellular distribution of RUNX2 and prostate‐associated proteins was assessed using immunofluorescence microscopy. In vivo Runx2 knock out was achieved by tamoxifen treatment of Nkx3.1CreERT; Runx2 loxp/loxp mice. Results Prostate epithelium‐derived spheroids, which are enriched in stem cells, were shown to contain elevated levels of Runx2 mRNA. Spheroid formation required Runx2 since adenovirus‐Cre mediated knockout of Runx2 in prostatic epithelial cells from Runx2 loxp/loxp mice severely reduced spheroid formation and stem cell markers while Runx2 overexpression was stimulatory. In vivo, Runx2 was detected during early prostate development (E16.5) and in adult mice where it was present in basal and luminal cells of ventral and anterior lobes. Prostate‐selective deletion of Runx2 in tamoxifen‐treated Nkx3.1CreERT; Runx2 loxp/loxp mice severely inhibited growth and maturation of tubules in the anterior prostate and reduced expression of stem cell markers and prostate‐associated genes. Conclusion This study demonstrates an important role for Runx2 in prostate development that may be explained by actions in prostate epithelial stem cells.