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Distinct in vivo expression patterns of survivin splice variants in renal cell carcinomas
Csaba Mahotka1, Thomas Krieg, Andreas Krieg
1Institute of Pathology, Heinrich Heine-University, Duesseldorf, Germany.
Abstract:
Survivin, a novel member of the inhibitor of apoptosis protein (IAP) family, reduces the susceptibility of tumor cells to proapoptotic stimuli, thereby promoting tumor cell survival during tumor progression and treatment with anticancer drugs. Recently, we identified 2 novel alternative splice variants of survivin, survivin-2B and survivin-Delta Ex3, which differ in their antiapoptotic properties. Survivin-2B has lost its antiapoptotic potential and may act as a naturally occurring antagonist of antiapoptotic survivin and survivin-Delta Ex3. Because the in vivo expression of these splice variants in human cancer has not been analyzed so far, 57 renal cell carcinomas (RCCs) were explored using quantitative reverse transcriptase polymerase chain reaction. We found that all RCCs express survivin-Delta Ex3, survivin-2B and survivin, the latter being the dominant transcript. When we compared early and intermediate stages with late stages of clear cell RCCs, no significant changes in the expression levels of survivin and survivin-Delta Ex3 became evident. However, a significant decrease was observed for the mRNA ratio between survivin-2B and survivin in late tumor stages (p = 0.036). Chromophilic/papillary RCCs, which are known to be less aggressive than clear cell RCCs, did not show significantly lower expression levels of antiapoptotic survivin and survivin-Delta Ex3, compared with stage-adjusted clear cell RCCs. Our study demonstrates for the first time in vivo expression of functionally different survivin variants and suggests a role of these survivin splice variants in the progression and clinical behavior of human RCCs.
Insights
This study analyzed survivin splice variants in renal cell carcinoma (RCC). Survivin-2B and survivin-Delta Ex3 are expressed in RCC, with survivin-2B decreasing in late stages, suggesting a role in tumor progression.
Area of Science:
- Molecular Biology
- Cancer Research
- Oncology
Background:
- Survivin, an inhibitor of apoptosis protein (IAP), promotes tumor cell survival.
- Two novel splice variants, survivin-2B and survivin-Delta Ex3, exhibit different antiapoptotic properties.
- Survivin-2B may antagonize the antiapoptotic effects of survivin and survivin-Delta Ex3.
Purpose of the Study:
- To investigate the in vivo expression of survivin splice variants in human renal cell carcinoma (RCC).
- To determine the correlation between survivin variant expression and RCC progression and clinical behavior.
Main Methods:
- Quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was used.
- Expression levels of survivin, survivin-2B, and survivin-Delta Ex3 were analyzed in 57 RCC samples.
- Comparison of expression between different RCC stages and subtypes.
Main Results:
- All analyzed RCCs expressed survivin-Delta Ex3, survivin-2B, and survivin, with survivin being the dominant transcript.
- No significant changes in survivin and survivin-Delta Ex3 expression were observed between early/intermediate and late stages of clear cell RCC.
- A significant decrease in the mRNA ratio of survivin-2B to survivin was noted in late-stage clear cell RCC (p = 0.036).
- Chromophilic/papillary RCCs did not exhibit significantly lower expression of survivin and survivin-Delta Ex3 compared to stage-matched clear cell RCCs.
Conclusions:
- This study provides the first in vivo analysis of functionally distinct survivin splice variants in human RCC.
- The findings suggest a potential role for survivin splice variants in the progression and clinical characteristics of RCC.
- Survivin-2B's decreasing expression in advanced RCC warrants further investigation into its role as a potential tumor suppressor or antagonist.