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

ABSTRACT

BACKGROUND: C/EBPalpha is a critical mediator of terminal differentiation and a tumor suppressor through its strong antiproliferative actions on cell cycle regulatory proteins. C/EBPalpha also appears to regulate androgen receptor (AR) AR signaling. There, is a paucity of information on the expression and sub-cellular localization of C/EBPalpha 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/EBPalpha 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/EBPalpha mRNA was expressed at all ages. In humans, C/EBPalpha showed prominent nuclear localization from peripubescence up to middle age but was sequestered in the cytosol in older individuals; the mRNA level for C/EBPalpha remained essentially unchanged. Most prostate adenocarcinomas expressed a range of levels of C/EBPalpha mRNA and protein that were relatively high in metastatic tumors in a manner that correlated with AR expression; however, most cells showed C/EBPalpha sequestered in the cytosol. CONCLUSIONS: Temporal changes in sub-cellular localization of C/EBPalpha are consistent with a role in prostate differentiation and as a prostate tumor suppressor; the cytoplasmic sequestration of C/EBPalpha, unique to older human prostates, is arguably a permissive condition for the greater frequency of proliferative disorders of the prostate. In malignant prostate C/EBPalpha may be available to regulate AR signaling through transient changes in its sub-cellular localization.