Survivin and its spliced isoform gene expression is associated with proliferation of renal cancer cells and clinical stage of renal cancer.
BACKGROUND
Survivin has been implicated in inhibition of apoptosis. To date, alternatively spliced isoforms, Survivin-2alpha, -2B, -DeltaEx3, -3B, have been described. We assessed the effect of survivin gene expression on the proliferation of renal cancer (RCC) cells, and studied the association of survivin and its spliced isoform gene expression levels with the clinical stage of RCC.


METHODS
Gene expression of survivin and its spliced isoform in RCC cells, Caki-1, were performed by RT-PCR. We knocked down the gene expression of Survivin using small interfering RNA (siRNA), and assessed the cell proliferation by MTS assay. Next, we quantified the gene expression levels of survivin and its isoform in nephrectomy samples using quantitative real-time PCR.


RESULTS
In Caki-1 cells, survivin and survivin-2alpha, -2B were expressed higher than survivin-DeltaEx3. Decrease of Survivin gene expression by transfection of siRNA was accompanied by inhibition of the proliferation of Caki-1 cell with 36% decrease in comparison with negative control transfected cells (p<0.01). In clinical RCC tissues, survivin expression levels in metastatic stage were significantly higher compared with those in distant metastasis stage (M0:M1=1:4.81, p=0.014); survivin 2B gene expression levels in pT3 tumors were associated significantly higher than those in pT1 (pT1:pT3=1:4.50, p=0.043). No significant differences were found in survivin-2alpha expression levels and the ratio of survivin-2B/survivin gene expression levels among any clinical stages.


CONCLUSIONS
We first demonstrated the gene expression of survivin-2alpha in renal cancer cells, and also showed that survivin and its spliced isoforms had associations with renal cancer cell proliferation and distant metastases.
Okamura
Keigo
K
Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Koike
Hidekazu
H
Sekine
Yoshitaka
Y
Matsui
Hiroshi
H
Suzuki
Kazuhiro
K
D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D049109:Cell Proliferation; D015853:Cysteine Proteinase Inhibitors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D000077022:Survivin; D014162:Transfection; D014407:Tumor Cells, Cultured
C107489:BIRC5 protein, human; D015853:Cysteine Proteinase Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000077022:Survivin