Abstract
The molecular mechanism that controls the proliferation and differentiation of prostate epithelial cells is currently unknown. We previously identified a 44-kDa protein (p44/wdr77) as an androgen receptor-interacting protein that regulates a set of androgen receptor target genes in prostate epithelial cells and prostate cancer. In this study, we found that p44 localizes in the cytoplasm of prostate epithelial cells at the early stage of prostate development when cells are proliferating, and its nuclear translocation is associated with cellular and functional differentiation in adult prostate tissue. We further demonstrated that cytoplasmic p44 protein is essential for proliferation of prostate epithelial cells, whereas nuclear p44 is required for cell differentiation and prostate- specific protein secretion. These studies suggest a novel mechanism by which proliferation and differentiation of prostate epithelial cells are controlled by p44’s location in the cell.
Highlights
During development of a multicellular organism, cells proliferate for a defined length of time before they begin functional differentiation [1,2,3]
We have demonstrated that cytoplasmic p44 is essential for proliferation whereas nuclear p44 is required for differentiation of
P44 is in abundance in the cytoplasm of prostate epithelial cells harvested from mice during the early stages of development, when cells are proliferating, and in growing immortalized temperature-sensitive lung epithelial cells ts
Summary
During development of a multicellular organism, cells proliferate for a defined length of time before they begin functional differentiation [1,2,3]. Development of the prostate gland is a dynamic process in which epithelial cells proliferate and functionally differentiate [4,5]. Androgen signaling through the androgen receptor (AR) induces the growth of the prostate epithelium in early development [6] and is required later for the production of prostate-secreted proteins [7]. Other factors (NKX3.1, Hox, FoxA, Shh, Sox, Fgf7/10, Wnt5a, Bmp4/7, and Notch1) affect ductal morphology, budding, and branching of epithelium during mouse prostate development [5]. The molecular mechanism that determines the timing of prostate epithelial proliferation and differentiation is currently unknown
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