期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：25
页码：9375-9380
DOI：10.1073/pnas.0403041101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
