Gene Expression of Survivin and Its Spliced Isoforms Associated With Proliferation and Aggressive Phenotypes of Prostate Cancer

Abstract

To assess the effect of survivin gene expression on the proliferation of prostate cancer (PCa) cells and study the association of suvivin and its spliced isoforms gene expression levels with the pathologic grade of PCa. Gene expression of survivin and its spliced isoforms in the LNCaP and PC-3 PCa cell lines was determined using reverse transcriptase-polymerase chain reaction. We knocked down the gene expression of survivin using small interfering RNA and assessed the cell proliferation using the MTS assay. Next, we quantified the gene expression levels of survivin and its isoforms in prostate biopsy samples (PCa, n = 37; benign prostatic hyperplasia, n = 13; PCa after androgen deprivation therapy, n = 12) using the quantitative real-time polymerase chain reaction method. In PCa cells, survivin and survivin-2alpha and survivin-2B were expressed more than survivin-DeltaEx3. The decrease in survivin gene expression by transfection of siRNA was accompanied by the inhibition of cell proliferation of PCa cells (31% and 25% decreased in LNCaP and PC-3 cells, P <0.01). In the prostate biopsy samples, the survivin expression in PCa was significantly greater than that in BPH or PCa after androgen deprivation therapy (PCa, 1; BPH, 0.16; PCa after androgen deprivation therapy, 0.27; P <0.01). In the PCa samples, the survivin expression level was associated significantly with high-grade cancer (Gleason score 8 or 9; Gleason score 7 versus 8 or 9, 1 versus 2.00, respectively; P <0.05). The survivin-2B/survivin ratio in high-grade cancer was lower than that in low-grade (Gleason score 7) cancer (Gleason score 7 versus 8 or 9, 1 versus 0.69; P <0.10). These findings suggest that survivin and its spliced isoforms have associations with PCa cell proliferation and aggressive phenotypes.