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Differential Expression of S100A2 and S100A4 During Progression of Human Prostate Adenocarcinoma

Sanjay Gupta, Tajamul Hussain, Gregory T. MacLennan, Pingfu Fu, Jigar Patel, Hasan Mukhtar

From the Departments of Urology, Pathology, Epidemiology, and Biostatistics, Case Western Reserve University and The Research Institute of University Hospitals of Cleveland, Cleveland, OH; Department of Dermatology, University of Wisconsin-Madison, Madison, WI.

Address reprint requests to Hasan Mukhtar, PhD, Department of Dermatology, University of Wisconsin, Medical School Center, Room B25, 1300 University Avenue, Madison, WI 53706; email: hmukhtar{at}wisc.edu.

Purpose: To establish the clinical significance of calcium binding proteins S100A2 and S100A4 during progression of human prostate adenocarcinoma.

Patients and 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 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.

Conclusion: Loss of S100A2 and increased expression of S100A4 may be an important event during progression of prostate cancer in humans.

Supported by the funds from United States Public Health Services Grants RO1 CA78809, American Institute for Cancer Research Grants 00A030, and Department of Defense Grant DAMD 17-00-1-0527.

S.G. and T.H. contributed equally to this work.

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