Expression and sub-cellular localization of the CCAAT/enhancer binding protein Α in relation to postnatal development and malignancy of the prostate

Abstract

Background C/EBPΑ is a critical mediator of terminal differentiation and a tumor suppressor through its strong antiproliferative actions on cell cycle regulatory proteins. C/EBPΑ also appears to regulate androgen receptor (AR) AR signaling. There, is a paucity of information on the expression and sub-cellular localization of C/EBPΑ in normal mouse and human prostate and in prostate cancer. Methods Immunohistochemistry of tissues including tissue arrays, quantitative polymerase chain reaction and mRNA expression database mining. Results In the mouse prostate epithelium, C/EBPΑ was present at 1 week postnatal localized in the cytosol, began to show nuclear localization at 8 weeks and continued to show prominent nuclear expression at 10 weeks and beyond; C/EBPΑ mRNA was expressed at all ages. In humans, C/EBPΑ showed prominent nuclear localization from peripubescence up to middle age but was sequestered in the cytosol in older individuals; the mRNA level for C/EBPΑ remained essentially unchanged. Most prostate adenocarcinomas expressed a range of levels of C/EBPΑ mRNA and protein that were relatively high in metastatic tumors in a manner that correlated with AR expression; however, most cells showed C/EBPΑ sequestered in the cytosol. Conclusions Temporal changes in sub-cellular localization of C/EBPΑ are consistent with a role in prostate differentiation and as a prostate tumor suppressor; the cytoplasmic sequestration of C/EBPΑ, unique to older human prostates, is arguably a permissive condition for the greater frequency of proliferative disorders of the prostate. In malignant prostate C/EBPΑ may be available to regulate AR signaling through transient changes in its sub-cellular localization. Prostate 68: 1206–1214, 2008. © 2008 Wiley-Liss, Inc.