p44 Functions in Prostate Epithelial Cells Figure 2. P44 nuclear translocation is associated with the decrease in cell proliferation during prostate development. (A) Proliferation rate of prostate epithelial cells is decreased during mouse development. BrdU was injected into mice, and 3 days later, inmmunostaining with anti- BrdU antibody was performed on the anterior (AP) and dorsal lateral (DLP) prostates to identify BrdU-positive (proliferating) prostate epithelial cells (in brown). (B) The quantitative data of proliferative epithelial cells in the AP or DLP prostate are shown. Numbers in parentheses indicate the percentages of BrdU-positive epithelial cells. One-way ANOVA analysis: F = 873.4, p,0.0001, R square = 0.9976. The p values of unpaired Student’s t- Test of data between 7–10 d and 14–17 d and between 30 d and 60 d are ,0.0001 and 0.0060, respectively. doi:10.1371/journal.pone.0049173.g002 expression led to the differentiation of lung epithelial cells [26]. However, p44 is not required for differentiation of lung epithelial cells. In this report, we demonstrate that cytoplasmic p44 is essential for prostate epithelial cell growth, whereas nuclear p44 promotes cell differentiation and prostate secretory protein expression. This research reveals a novel mechanism by which the proliferation and differentiation of prostate epithelial cells are determined. Results P44 Nuclear Translocation is Associated with Functional Differentiation and Growth Arrest in Prostate Epithelial Cells Previous work showed that p44 localizes in the cytoplasm of prostate epithelial cells during the early (,28 days) stage of mouse PLOS ONE | www.plosone.org 3 November 2012 | Volume 7 | Issue 11 | e49173