Down regulation of PSA by C/EBPalpha is associated with loss of AR expression and inhibition of PSA promoter activity in the LNCaP cell line.
BACKGROUND
C/EBPalpha is a transcription factor essential for terminal differentiation of several cell types. It has not known if C/EBPalpha protein is expressed and functions in the prostate gland.


METHODS
The presence of C/EBPalpha in normal and cancerous prostate epithelium was examined by immunochemistry. Over expression of C/EBPalpha in LNCaP cells was conducted with retrovirus-mediated transduction. PSA expression was examined by RT-PCR and western blot and PSA promoter activity by luciferase reporter assay.


RESULTS
In normal prostate C/EBPalpha was expressed in the basal layer of the epithelium. In prostate cancer C/EBPalpha was detected at low levels throughout the cancers and in advanced prostate cancer C/EBPalpha expression was associated with decreased expression of AR and PSA. Overexpression of C/EBPalpha inhibited epigenetically PSA expression and was accompanied by the loss of expression of AR. Transient increase of C/EBPalpha inhibited the PSA promoter/enhancer activity independently of expression of AR.


CONCLUSIONS
In LNCaP cells C/EBPalpha over expression inhibits expression of PSA by AR -dependent and independent mechanisms and by extinguishing AR expression provides a model for hormonal independent cell growth.
Yin
Hong
H
Feist-Weiller Cancer Center and Department of Medicine, LSU Health Sciences Center, Shreveport, LA, USA. hyin@lsuhsc.edu
Radomska
Hanna S
HS
Tenen
Daniel G
DG
Glass
Jonathan
J
D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011467:Prostate / Q000378:metabolism; D017430:Prostate-Specific Antigen / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011944:Receptors, Androgen / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics
D022763:CCAAT-Enhancer-Binding Protein-alpha; D020033:Protein Isoforms; D011944:Receptors, Androgen; D017430:Prostate-Specific Antigen