Expression and sub-cellular localization of the CCAAT/enhancer binding protein alpha in relation to postnatal development and malignancy of the prostate.
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.
Zhang
Juan
J
Department of Biochemistry and Cancer Biology, Medical University of Ohio, Toledo, Ohio 43614, USA.
Wilkinson
John Erby
JE
Gonit
Mesfin
M
Keck
Rick
R
Selman
Steven
S
Ratnam
Manohar
M
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics* / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D020411:Oligonucleotide Array Sequence Analysis; D011467:Prostate / Q000254:growth & development* / Q000473:pathology / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D022763:CCAAT-Enhancer-Binding Protein-alpha; D012333:RNA, Messenger; D011944:Receptors, Androgen