Differential expression of S100A2 and S100A4 during progression of human prostate adenocarcinoma.
OBJECTIVE
To establish the clinical significance of calcium binding proteins S100A2 and S100A4 during progression of human prostate adenocarcinoma.


METHODS
Expression pattern of S100A2 and S100A4 was determined in normal human prostate epithelial cells (NHPE); virally transformed prostate epithelial cells (PZ-HPV-7); several human prostate carcinoma cells (22Rv1, DU145, LNCaP, and PC3); tissue samples obtained during transuretheral prostatic resection from patients with benign prostate hyperplasia (BPH), prostatitis, and adenocarcinoma; and paraffin-embedded sections from pair-matched benign and cancer specimens of different tumor grade.


RESULTS
High constitutive protein expression of S100A2 was observed in NHPE and PZ-HPV-7 cells, whereas its complete absence was observed in 22Rv1, DU145, LNCaP, and PC3 cells. Tissue samples of BPH and prostatitis exhibited higher mRNA and protein levels of S100A2 than low-grade cancer (Gleason score <or= 6), whereas a complete loss was observed in high-grade cancer specimens (Gleason score > 6). Immunohistochemical analysis further confirmed high levels of S100A2 in benign tissues and a progressive loss with increasing tumor grade. The protein level of S100A4 was significantly higher in all carcinoma cells compared with NHPE and PZ-HPV-7 cells. The mRNA and protein level of S100A4 was significantly higher in high-grade cancer specimens compared with BPH, prostatitis, and low-grade cancer. The high levels of S100A4 observed in cancer tissue correlated with increasing tumor grade.


CONCLUSIONS
Loss of S100A2 and increased expression of S100A4 may be an important event during progression of prostate cancer in humans.
Gupta
Sanjay
S
Department of Urology, Case Western Reserve University and The Research Institute of University Hospitals of Cleveland, Cleveland, OH, USA.
Hussain
Tajamul
T
MacLennan
Gregory T
GT
Fu
Pingfu
P
Patel
Jigar
J
Mukhtar
Hasan
H
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016022:Case-Control Studies; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D016555:Matched-Pair Analysis; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000378:metabolism*; D018709:Statistics, Nonparametric
D014408:Biomarkers, Tumor; D002630:Chemotactic Factors; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C098997:S100A2 protein, human; C077591:S100A4 protein, human