Our working group has previously shown that bile acids (BAs) accelerate carcinogenic
processes in pancreatic cancer (PC) in which mucin 4 (MUC4) expression has a central
role. However, the role of other mucins in PC are less clear, especially in bile-induced
cancer progression. The study aim was to investigate expression of MUC17 in BAs- or
human serum-treated pancreatic ductal adenocarcinoma (PDAC) cell lines and use different
assays with RNA silencing/overexpression to study the role of MUC17 in cancer progression.
Protein expression of MUC17 was evaluated in 55 human pancreatic samples by immunohistochemistry,
and Kaplan-Meier survival analysis was used to compare survival curves. Expression
of MUC17 increased in PDAC patients, especially in obstructive jaundice (OJ) and the
elevated MUC17 expression associated with poorer overall survival (10.66±1.99 vs.
15.05±2.03 months; Log rank: 0.0497). Treatment of Capan-1 and AsPC-1 cells with BAs
or with human serum obtained from PDAC + OJ patients enhanced the expression of MUC17,
as well as the proliferative potential of the cells, whereas knockdown of MUC17 alone
or in combination with MUC4 decreased BAs-induced carcinogenic processes. Our results
demonstrated that MUC17 has a central role in bile-induced PC progression, and in
addition to MUC4, this isoform also can be used as a novel prognostic biomarker.
