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Abstract
Background: Survivin is involved in the regulation of cell division and survival, two key processes in cancer. The majority of studies on survivin in colorectal cancer (CRC) have focused on protein expression and less is known about the expression of survivin splicing variants or survivin gene polymorphisms in CRC. In the present study, the mRNA levels of the five known isoforms of survivin as well as survivin protein were assessed in matched normal and neoplastic colorectal tissue. Moreover, the 9386C/T and −31G/C polymorphisms were investigated.Methods: Quantitative RT-PCR was used to assess mRNA levels in fresh/frozen tissue samples. Protein levels were immunohistochemically evaluated on formalin-fixed paraffin-embedded tissue sections. Individuals were genotyped using real time PCR.Results: Expression of all 5 survivin splice variants as well as survivin protein was elevated in colorectal carcinomas compared to normal tissue. Specific splice variant expression differentially correlated with clinicopathological parameters. Furthermore, both snps correlated with splice variant levels or their ratios in colorectal carcinomas while the −31G/C snp may be related to CRC development and improved overall survival.Conclusion: Our results support a role of survivin in colorectal carcinogenesis while the −31G/C snp may constitute a marker of survival.
Highlights
Survivin is a unique member of the family of the Inhibitors of Apoptosis Proteins (IAPs) as it carries a single baculoviral IAP repeat (BIR) domain
No significant difference was observed in the expression levels between males and females and between patients with positive or negative lymph nodes. mRNA expression of survivin-2B significantly correlated with tumor grade with levels being higher in well differentiated compared to moderately and poorly differentiated tumors (Tables 3 and 4)
Most studies of survivin in colorectal cancer (CRC) have focused on protein expression and less is known about the expression of survivin splicing variants or survivin gene polymorphisms in CRC
Summary
Survivin is a unique member of the family of the Inhibitors of Apoptosis Proteins (IAPs) as it carries a single baculoviral IAP repeat (BIR) domain. Survivin has lately drawn much attention due to its involvement in many cellular processes. It functions as a central regulator of cell division as it has been shown to promote mitotic progression and G1/S transition in cancer cells [19,20]. It is not expressed or is present at low levels in normal differentiated tissues, whereas it is highly expressed in many tumors including breast, lung and colon [1,13,26,33]. The majority of studies on survivin in colorectal cancer (CRC) have focused on protein expression and less is known about the expression of survivin splicing variants or survivin gene polymorphisms in CRC. The 9386C/T and −31G/C polymorphisms were investigated
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