AIM: To investigate the expression of Survivin in pancreatic cancer and its correlation to the expression of Bcl-2.

METHODS: Survivin and Bcl-2 expressions were examined by immunohistochemistry in 42 tissue samples from pancreatic cancer and 10 from normal pancrease.

RESULTS: No survivin expression was detected in the tissue samples from normal pancrease, while it was detected in 34 of 42 tissue samples from pancreatic cancer (81.95%). There was a correlation between survivin expression and differentiation and stages of pancreatic cancer. Survivin positive cases were strongly correlated to Bcl-2 expression (28/30 vs 6/12, P < 0.05).

CONCLUSION: Overexpression of survivin plays an important role in the development and progression of pancreatic cancer, and correlates to the expression of Bcl-2. Survivin expression can be used as a prognostic factor.

The inhibitor of apoptosis protein (IAP) is a member of the widely-expressed gene family of apoptosis inhibitors. It can inhibit apoptosis induced by a variety of stimuli and plays a critical role in the physiologic activities of cells. Survivin is a recently-characterized gene, a member of the IAP family, and has a close relation between anti-apoptosis and tumors. Overexpression of survivin has been reported to play an important role in the development and progression of pancreatic cancer[1-5]. In this study, we investigated the relationship between the expression of survivin in patients with pancreatic cancer and the expression of Bcl-2 in order to provide a theoretical basis for the prevention, diagnosis, and treatment of pancreatic cancer.

Survivin, a recently-characterized member of IAP family, was isolated from the human gene bank by Altieri et al[6] in 1997 using effector cell protease receptor-1 (EPR-1) cDNA. Recently, great progress has been made in the structure and function of survivin and its correlation to malignant tumors. Many findings have suggested that survivin may express selectively in different tissues. Survivin was max expressed or poorly expressed in normal terminally-differentiated tissues, whereas it was extensively expressed in many kinds of human tumor tissues[7-14].

Studies have shown that Caspase is responsible for apoptosis, which can activate in cascade and lyze protein, thus determining the pattern of apoptosis. Survivin could directly inhibit the activities of Caspase-3 and 7 and block the process of apoptosis and indirectly inhibit Caspase through P21.Therefore survivin would bind to cell cycle apoptosis factor CDK4 to form survivin-CDK4 complex, and then release of P21 from CDK4 complex.When P21 was bound to mitochondrial Caspase-3, it could inhibit its activity, thus preventing apoptosis[15-17].

The results of our study showed that survivin was highly expressed in pancreatic tumor tissues, but not in normal pancreatic tissues, suggesting that it might play a critical role in the development and progression of pancreatic cancer. Furthermore, there was a positive correlation between survivin expression and tumor TNM staging and differentiation grade. It can be concluded that survivin expression is indicative of higher invasiveness or poor prognosis in pancreatic cancer.

Bcl-2 was the first characterized anti-apoptotic gene with an inhibiting apoptotic pathway different from that of survivin. Bcl-2 could regulate apoptosis by preventing cytochrome C release from mitochondrion to cytoplasm. Whereas, survivin acted by direct inhibition of the terminal effector proteases of apoptosis, i.e., Caspase-3 and Caspase-7.

Our study demonstrated that the expression of survivin was positively correlated with that of Bcl-2. It might be caused by the same transcription and activation mechanism of survivin and Bcl-2, or both might be regulated by GC-rich promoters, and were then transcripted and activated to enhance cell proliferation, acting synergistically to inhibit apoptosis[18-29].

Asanuma et al[2,5] investigated whether survivin expression could directly regulate cancer sensitivity to radiotherapy using gene-transducted pancreatic cancer cell strain (MIAPaCa-2). Their results showed that survivin expression could directly down-regulate pancreatic cancer sensitivity to radiotherapy.

In addition, Rohayem et al[12,18,31] observed that specific anti-survivin antibody could be detected in serum of patients with cancers of the lung and colon, suggesting that this antibody could be used as a new diagnostic marker for cancers of the lung and colon. Furthermore, Smith et al[31], Moore et al[32], and Swana et al[33] found that survivin levels in urine could be used to diagnose primary and recurrent bladder carcinomas, thus providing a new idea for the diagnosis of pancreatic cancer[34-38].

In conclusion, Survivin can be used as a cancer therapeutic target because of its selective expression in the tissue concerned. Moreover, natural antisense nucleic acid for Survivin-endogenous EPR-1 has become a new hot issue for the tumor gene therapy.