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

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.

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.

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.

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.