The expression of ICE in pancreatic carcinoma

Background: ICE: is a cysteine protease that cleaves inactive pro-IL-1 beta to generate the active proinflammatory cytokine IL-1 beta. Recent studies suggest that ICE is also involved in programmed cell death (apoptosis). We investigated the expression of ICE in human adenocarcinomas of the pancreas and in the pancreatic carcinoma cell line As PC-1. Methods: Pancreatic carcinoma tissue from 42 patients were used for Western blot analyses and immunohistochemical staining of ICE, cyclin D1,EGF and E GF receptor. The pancreatic carcinoma cell line AsPC-1 was incubated with E GF or IFN-gamma for 24 h or 72 h and used for Western blot and cytometric c ell cycle analyses. Results: Immunohistochemistry and Western blot analyses of pancreatic tissu e revealed an overexpression of ICE in 71% and 80% of tumor cells, respecti vely. The overexpression of ICE in tumor cells correlated significantly wit h the overexperssion of cyclin D1 (P < 0.0005), epidermal growth factor, EG F (P<0.05) and EGF-receptor (P < 0.002). In the pancreatic carcinoma cell l ine AsPC-1 overexpression of ICE was induced by EGF or IFN-gamma. 20% of th e IFN-gamma-stimulated cells became apoptotic after 72 h, whereas EGF-stimu lated cells did not become apoptotic in the same time window. Conclusion: Our results suggest that ICE has a bivalent function and is inv olved in apoptotic as well as in antiapoptotic pathways. The partially anti apoptotic function of ICE in pancreatic carcinoma could explain the observe d overexpression of ICE in this aggressive tumor.