Abstract: Objective: To explore the role of ubiquitin-proteasome pathway for the gelsolin protein degradation in pancreatic cancer. Methods: Pancreatic cancer cell lines BxPC-3 and PANC-1 were first treated with specific 26s proteasome inhibitor lactacystin. Immunoblots of cell lysates were probed for gelsolin expression. To determine whether gelsolin was conjugated to ubiquitin, proteins extracted from the cells treated with or without lactacystin were immunoprecipitated with anti-gelsolin antibody, followed by Western blot analysis using anti-ubiquitin monoclonal antibody. Results: The expression of gelsolin protein increased obviously after treated with lactacystin in BxPC-3 cells for 12h. Using anti-gelsolin antibody to immunoprecipitate gelsolin protein and followed by Western blot using anti-ubiquitin monoclonal antibody, it was found that inhibition of proteasome pathway by lactacystin resulted in accumulation of ubiquitylated forms of gelsolin protein. In PANC-1 cell line, there were no significant changes of gelsolin after treatment with lactacystin. Conclusion: Ubiquitin-proteasome dependent degradation may be an important regulatory mechanism for gelsolin down-regulation in pancreatic cancer.

Key words: ubiquitin-proteasome pathway, gelsolin, pancreatic cancer