Axin2 expression identifies progenitor cells in the murine prostate.
BACKGROUND
We previously reported that prostatic stem/progenitor cells are concentrated in the proximal region of prostatic ducts and express stem cell antigen 1 (Sca-1). As Wnt signaling is important for the maintenance of stem cells, we determined whether Sca-1 expressing cells also express Axin2, as Axin2 expression is highly suggestive of active Wnt signaling.


METHODS
Axin2 promoter reporter mice were used for whole mount and fluorescence activated cell sorting (FACS) analysis to determine its expression in the prostate. Axin2 expressing cells were also examined for the co-expression of Sca-1. We also used a chemical activator of Wnt signaling, BIO, to determine the effects of Wnt signaling on the growth of primary prostate cells in vitro.


RESULTS
We show that Axin2 expression is present in all lobes and is regulated by androgens with the highest Axin2 expression in the lateral and dorsal prostate. Furthermore, a fraction of Axin2 expressing cells co-express Sca-1, suggesting that some progenitor cells have active Wnt signaling. Lastly, we demonstrate that activation of the Wnt pathway may result in increased growth, consistent with a role for Wnt signaling in maintenance and/or expansion of the progenitor cell population.


CONCLUSIONS
Axin2 expressing cells that co-express Sca-1 are present in all prostate lobes suggesting that progenitor cells reside within the Wnt active population. An understanding of the basic biology of signaling pathways mediating growth in the prostate may lead to rational therapies to treat benign prostatic hyperplasia and prostate cancer.
Ontiveros
Christopher S
CS
Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA. ontivc01@popmail.med.nyu.edu
Salm
Sarah N
SN
Wilson
E Lynette
EL
D000728:Androgens / Q000378:metabolism; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D060466:Axin Protein; D049109:Cell Proliferation; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011467:Prostate / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism
D000728:Androgens; D000950:Antigens, Ly; D060466:Axin Protein; C111729:Axin2 protein, mouse; D003598:Cytoskeletal Proteins; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D051153:Wnt Proteins; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3