Koike Hidekazu, Sekine Yoshitaka, Kamiya Makoto, Nakazato Haruki, Suzuki Kazuhiro
Department of Urology, Gunma University Graduate School of Medicine, Maeabshi City, Gunma, Japan.
Urology. 2008 Dec;72(6):1229-33. doi: 10.1016/j.urology.2007.12.064. Epub 2008 Mar 12.
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.
评估生存素基因表达对前列腺癌细胞增殖的影响，并研究生存素及其剪接异构体基因表达水平与前列腺癌病理分级的相关性。
采用逆转录-聚合酶链反应测定LNCaP和PC-3前列腺癌细胞系中生存素及其剪接异构体的基因表达。我们使用小干扰RNA敲低生存素的基因表达，并通过MTS法评估细胞增殖。接下来，我们采用定量实时聚合酶链反应方法对前列腺活检样本（前列腺癌，n = 37；良性前列腺增生，n = 13；雄激素剥夺治疗后的前列腺癌，n = 12）中生存素及其异构体的基因表达水平进行定量。
在前列腺癌细胞中，生存素、生存素-2α和生存素-2B的表达高于生存素-DeltaEx3。转染siRNA导致生存素基因表达降低，同时伴随着前列腺癌细胞增殖受到抑制（LNCaP和PC-3细胞分别降低31%和25%，P <0.01）。在前列腺活检样本中，前列腺癌组织中生存素的表达显著高于良性前列腺增生或雄激素剥夺治疗后的前列腺癌（前列腺癌，1；良性前列腺增生，0.16；雄激素剥夺治疗后的前列腺癌，0.27；P <0.01）。在前列腺癌样本中，生存素表达水平与高级别癌症显著相关（Gleason评分8或9；Gleason评分7与8或9相比，分别为1与2.00；P <0.05）。高级别癌症中生存素-2B/生存素的比值低于低级别（Gleason评分7）癌症（Gleason评分7与8或9相比，1与0.69；P <0.10）。
这些发现表明生存素及其剪接异构体与前列腺癌细胞增殖和侵袭性表型相关。
