Expression of apoptosis-related factors in human pancreatic duct cell carcinoma and intraductal papillary-mucinous tumor

Pancreatic duct cell carcinoma (PDQ is one of the most malignant of the gastrointestinal tumors. Expression of the apoptosis-related factors Fas ligand (FasL) and caspase-3 and the antiapoptotic factor survivin was examined in PDC and in intraductal papillary-mucinous tumor (IPMT) by reverse transcriptase-polymerase chain reaction (RT-PCR), immunoblot analysis, and immunohistochemistry. Frequent expression of FasL was observed in PDC. The co-culture experiments showed that PANC-1 cells induced apoptosis of Jurkat cells, whereas the PANC-1 cells themselves and jurkat cells cultured without the presence of PANC-1 showed few apoptotic changes. The immunoreactivity of caspase-3 was predominantly found in the cytoplasm of invasive tumors (PDC and invasive IPMT). There was a significant correlation between the cytoplasmic staining and malignant grade of the tumors. In contrast, the nuclear expression of this enzyme was significantly higher in noninvasive tumors than in invasive tumors. Survivin was more frequently expressed in malignant tumors than in benign tumors. In PDC, high levels of survivin expression were significantly associated with a reduction in the apoptotic index of the tumor cells. These findings suggest that: (1) Fas-L may play an important role in the ability of PDC to escape from immune surveillance through the induction of apoptosis in tumor-attacking lymphocytes; (2) cytoplasmic expression of caspase-3 may be related to the invasiveness of pancreatic tumors; and (3) the expression of survivin may be up-regulated during the development of cancer by reducing the cancer cell apoptosis.