Down-regulation of protein kinase, DNA-activated, catalytic polypeptide attenuates tumor progression and is an independent prognostic predictor of survival in prostate cancer.

OBJECTIVE

Protein kinase, DNA-activated, catalytic polypeptide (PRKDC) is a critical component of DNA repair machinery and its dysregulated expression has been observed in various cancer types or premalignant cells. However, its role in prostate cancer (PCa) development and its prognostic significance in PCa is unknown.

METHODS

The mRNA and protein levels of PRKDC were analyzed in 15 pairs of PCa and benign prostatic hyperplasia tissues as well as PCa cell lines by quantitative real-time polymerase chain reaction and Western blot, respectively. Small interfering RNA and short hairpin RNA-mediated knockdown of PRKDC, followed by cell proliferation, colony formation, and soft agar assays were performed. Xenograft mouse model was used to evaluate in vivo effects of PRKDC knockdown. The association between PRKDC expression and clinicopathologic features was assessed by χ tests. Kaplan-Meier analysis was performed to investigate the association between PRKDC expression and overall survival. Cox proportional hazards regression models were used to examine the prognostic significance of PRKDC.

RESULTS

Expression of PRKDC mRNA and protein was notably higher in PCa tissues and PCa cell lines. Knockdown of PRKDC markedly reduced cell proliferation, colony formation efficiency, and soft agar growth in DU145 cells. Down-regulation of PRKDC inhibited tumor growth of DU145 xenografts and enhance mice survival. In addition, PRKDC expression in PCa was significantly associated with Gleason score (P = 0.01), tumor stage (P = 0.028), and distant metastasis (P = 0.025). Patients with PCa having higher PRKDC expression had substantially shorter survival than patients with lower PRKDC expression.

CONCLUSION

Down-regulation of PRKDC attenuates tumor progression in PCa. PRKDC may potentially be a prognostic biomarker in PCa.