Activator protein 2α transcription factor expression is associated with luminal differentiation and is lost in prostate cancer

Purpose: Prostate cancer progression is associated with deregulation of genes like E-cadherin, p21/WAF1, MMP-2, VEGF, and IGF-binding protein, 3 and 5, all of which are target genes for the transcription factor activator protein 2α (AP-2α). We, therefore, hypothesize that the development/progression of prostate cancer is associated with changes in the expression of AP-2α. Experimental Design: We used immunofluorescent staining to assess the presence of AP-2α in normal, benign, and malignant human prostate tissues and to correlate its expression with tumor grade and stage. Results: We found that although AP-2α was expressed in normal prostate epithelium, it was not expressed in 30 prostate cancer specimens of different Gleason scores. Moreover, AP-2α protein was present in the luminal cell layer but not in the basal cell layer of the normal epithelium, which indicated that the loss of AP-2α staining in the prostate cancer specimens was not attributable to a lack of AP-2α-expressing cells. Further analysis demonstrated the presence of AP-2α in 2 (40%) of 5 atrophic normal epithelium, in 4 (24%) of 17 cases of benign prostatic hyperplasia, and in 2 (13%) of 13 cases of high-grade prostatic intraepithelial neoplasia. Loss or reduction in AP-2α expression was also observed in LNCaP, LNCaP-LN3, and PC3M-LN4 cell lines. Conclusions: Our data demonstrate that AP-2α expression is associated with normal luminal differentiation and that a loss of AP-2α expression occurs early in the development of prostate adenocarcinoma. Loss of AP-2α may lead to deregulation in AP-2α target genes that normally regulate cellular growth and differentiation.