Activator protein 2alpha transcription factor expression is associated with luminal differentiation and is lost in prostate cancer.
OBJECTIVE
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 2alpha (AP-2alpha). We, therefore, hypothesize that the development/progression of prostate cancer is associated with changes in the expression of AP-2alpha.


METHODS
We used immunofluorescent staining to assess the presence of AP-2alpha in normal, benign, and malignant human prostate tissues and to correlate its expression with tumor grade and stage.


RESULTS
We found that although AP-2alpha was expressed in normal prostate epithelium, it was not expressed in 30 prostate cancer specimens of different Gleason scores. Moreover, AP-2alpha 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-2alpha staining in the prostate cancer specimens was not attributable to a lack of AP-2alpha-expressing cells. Further analysis demonstrated the presence of AP-2alpha 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-2alpha expression was also observed in LNCaP, LNCaP-LN3, and PC3M-LN4 cell lines.


CONCLUSIONS
Our data demonstrate that AP-2alpha expression is associated with normal luminal differentiation and that a loss of AP-2alpha expression occurs early in the development of prostate adenocarcinoma. Loss of AP-2alpha may lead to deregulation in AP-2alpha target genes that normally regulate cellular growth and differentiation.
Ruiz
M
M
Department of Cancer Biology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
Troncoso
P
P
Bruns
C
C
Bar-Eli
M
M
D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000032:analysis*; D018450:Disease Progression; D004847:Epithelial Cells / Q000473:pathology; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000032:analysis; D008297:Male; D011467:Prostate / Q000737:chemistry; D017430:Prostate-Specific Antigen / Q000032:analysis; D011468:Prostatectomy; D011470:Prostatic Hyperplasia / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D012016:Reference Values; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000032:analysis*; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C493673:TFAP2A protein, human; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D007633:Keratins; D017430:Prostate-Specific Antigen