A role for protease-activated receptor-2 in pancreatic cancer cell proliferation.

Abstract

The protease-activated receptor-2 (PAR-2) is a G protein-coupled receptor that is cleaved and activated by trypsin and tryptase. The purpose of this study was to clarify the role of PAR-2 in proliferation of human pancreatic cancer cells. PAR-2 mRNA and protein expression were detected by RT-PCR and Western blotting in three cell lines, SW1990, Capan-2, and Panc-1. The PAR-2 agonist peptide, SLIGKV (25, 50 micro g/ml) and trypsin (10, 100 ng/ml) significantly increased cell proliferation. Enhancement of MAP kinase also was observed in cancer cells treated with SLIGKV and trypsin. In vivo, subcutaneous xenografted tumors showed significantly enhanced growth after treatment with SLIGKV. Tumor-associated trypsinogen (TAT) mRNA and protein expression was detected in SW1990 and Capan-2, suggesting autocrine trypsin production. PAR-2 activated by trypsin plays an important role in promoting proliferation of pancreatic cancer.

• Authors: Rie Shimamoto, Tetsuji Sawada, Yasutake Uchima, Masafumi Inoue, Kenjiro Kimura, Yoshito Yamashita, Nobuya Yamada, Tamahiro Nishihara, Masaichi Ohira, Kosei Hirakawa
• Journal: International journal of oncology (Int J Oncol) Vol. 24 Issue 6 Pg. 1401-6 (Jun 2004) ISSN: 1019-6439 [Print] Greece
• PMID: 15138580 (Publication Type: Journal Article)

Chemical References

• Oligopeptides
• RNA, Messenger
• Receptor, PAR-2
• seryl-leucyl-isoleucyl--glycyl-lysyl-valine
• Trypsinogen
• Mitogen-Activated Protein Kinases
• Trypsin

Topics

• Animals
• Autocrine Communication
• Blotting, Western
• Cell Division (drug effects)
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mitogen-Activated Protein Kinases (metabolism)
• Oligopeptides (toxicity)
• Pancreatic Neoplasms (metabolism, pathology)
• RNA, Messenger (genetics, metabolism)
• Receptor, PAR-2 (agonists, genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Transplantation, Heterologous
• Trypsin (pharmacology)
• Trypsinogen (genetics, metabolism)
• Tumor Cells, Cultured