Estrogen receptor beta 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 beta (ER beta). To investigate the causes of this phenomenon, we measured cellular proliferation and apoptosis in VP of ER beta(-/-) and WT mice. With BrdUrd labeling, the number of proliferating cells was 3.6-fold higher in ER beta(-/-) 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 ER beta(-/-) 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 ER beta(-/-) 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 ER beta(-/-) mice, showing a shift of CK 19-positive cells toward a cell population of intermediate size and granularity. We conclude that, in ER beta(-/-) 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 ER beta signaling.
Imamov
Otabek
O
Department of Medical Nutrition, Karolinska Institute, Novum, S-141 86 Huddinge, Sweden.
Morani
Andrea
A
Shim
Gil-Jin
GJ
Omoto
Yoko
Y
Thulin-Andersson
Christina
C
Warner
Margaret
M
Gustafsson
Jan-Ake
JA
D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D004847:Epithelial Cells / Q000166:cytology*; D047629:Estrogen Receptor beta; D005434:Flow Cytometry; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D011467:Prostate / Q000166:cytology*; D011960:Receptors, Estrogen / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D047629:Estrogen Receptor beta; D011960:Receptors, Estrogen