Estrogen Receptor β Regulates Epithelial Cellular Differentiation in the Mouse Ventral Prostate

We have previously reported epithelial cellular hyperplasia in ventral prostates (VP) of mice lacking estrogen receptor β (ERβ). To investigate the causes of this phenomenon, we measured cellular proliferation and apoptosis in VP of ERβ-/-and WT mice. With BrdUrd labeling, the number of proliferatin...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2004-06, Vol.101 (25), p.9375-9380
Main Authors: Imamov, Otabek, Morani, Andrea, Shim, Gil-Jin, Omoto, Yoko, Thulin-Andersson, Christina, Warner, Margaret, Gustafsson, Jan-Åke
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Biological Sciences
Cell Differentiation
Cellular differentiation
Epithelial cells
Epithelial Cells - cytology
Epithelium
Estrogen Receptor beta
Estrogens
Flow Cytometry
Granularity
Hyperplasia
In Situ Nick-End Labeling
Male
Medical research
Medicin och hälsovetenskap
Mice
Mice, Knockout
Polymerase Chain Reaction
Population size
Prostate
Prostate - cytology
Prostate cancer
Receptors, Estrogen - deficiency
Receptors, Estrogen - genetics
Receptors, Estrogen - physiology
Rodents
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Summary:We have previously reported epithelial cellular hyperplasia in ventral prostates (VP) of mice lacking estrogen receptor β (ERβ). To investigate the causes of this phenomenon, we measured cellular proliferation and apoptosis in VP of ERβ-/-and WT mice. With BrdUrd labeling, the number of proliferating cells was 3.6-fold higher in ERβ-/-mice. There was also a decrease in apoptosis as measured by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling assay and an increase in expression of the anti-apoptotic bcl-2. The state of differentiation of the epithelial cells of the VP was studied by immunohistochemical staining, Western blotting, and fluorescence-activated cell sorting (FACS). In ERβ-/-mouse VP, the number of p63-positive cells (basal phenotype) was 2.6-fold higher, and expression level of cytokeratin (CK) 8, a luminal cell marker, was lower. FACS analysis with p63 showed that in WT mice the ratio of basal to intermediate/luminal cell populations expressing p63 was 1:2.5, whereas in ERβ-/-mice it was 1:9. The expression of basal/intermediate marker CK 19 in three FACS areas, g1, g2, and g3, gated according to cellular size and granularity, was 1:0.6:2 in WT and 1:4:6.7 in ERβ-/-mice, showing a shift of CK 19-positive cells toward a cell population of intermediate size and granularity. We conclude that, in ERβ-/-mouse VP, there is increased epithelial proliferation, decreased apoptosis, and accumulation of incompletely differentiated cells in an intermediate pool. The continued proliferation of intermediate cells leads to the prostatic epithelial hyperplasia observed in the absence of ERβ signaling.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0403041101