Abstract
Pancreatic cancer is the fourth leading cause of cancer-associated mortality in developed countries. Pancreatic ductal adenocarcinoma (PDAC) accounts for ~90% of all pancreatic cancer cases. The Notch signaling pathway serves a crucial role in embryonic development, as well as during the tumorigenesis of different types of cancer. However, Notch signaling serves either oncogenic or tumor suppressor roles depending on the tissue type. There are four Notch receptors (Notch1-4) and five ligands [Jagged1, Jagged2, δ-like ligand protein (DLL)1, DLL3 and DLL4]; therefore, it has been suggested that the different Notch receptors serve distinct roles in the same type of tissue. To determine whether this is the case, the present study measured the expression of all Notch receptors and their ligands in PDAC tissue samples and cells. Immunohistochemistry was performed to measure the expression of Notch receptors and their ligands in paraffin-embedded PDAC tissue samples. Immunofluorescence was used to detect the expression of Notch receptors in the pancreatic cancer cell lines human pancreatic adenocarcinoma (HPAC) and PANC-1. In addition, levels of Notch receptors and ligands in HPAC and PANC-1 cells were analyzed by western blot analysis. The results revealed that levels of Notch1 and Notch3 were increased in PDAC tissues, whereas levels of Notch2 and Notch3 were not. The expression of Notch receptors in the pancreatic cancer cell lines HPAC and PANC-1 was consistent with their expression in PDAC tissues. Additionally, levels of the ligands DLL1, DLL3 and DLL4 were increased in HPAC and PANC-1 cells, as well as PDAC tissue samples. However, the expression of Jagged1 and 2 remained low. These results indicate that Notch1, Notch3, DLL1, DLL3 and DLL4 are upregulated in PDAC, a positive correlation was observed between the expression of Notch1 and Notch3, and between Notch1 and the ligands DLL1, DLL3 and DLL4. whereas Notch2, Notch4, Jagged1 and Jagged2 are not. The interaction of Notch1 and Notch3 with Notch ligands DLL1, DLL3 and DLL4 may be important in maintaining the tumor phenotype of pancreatic cancer.