[The role of p38 MAPK in gastrin-induced u-PA expression in human colon cancer cells].

Abstract

OBJECTIVE:

To study the effect of gastrin on the mRNA and protein expression of urokinase-type plasminogen activator (u-PA) in human colon cancer cells and detect the role of p38 MAPK in this process.

METHODS:

Lipofectin method was used to transfect pCR3. 1/CCK2R vector expressing gastrin receptor into a colon cancer cell line colo320. Gastrin and gastrin antagonist were used to up-regulate and down-regulate the signaling pathway, respectively. Human colon cancer colo320 cells and colo320/ CCK2,R cells were cultured and then stimulated with gastrin for different time; SB203580 was added into culture medium to prevent p38 kinase pathway before incubating with gastrin; Western blot and RT-PCR were used to examine the u-PA expression. Western blot was employed to detect p38 kinase phosphorylation.

RESULTS:

Gastrin increased evidently the mRNA and protein expressions of u-PA and induced p38 kinase phosphorylation in colo320/CCK,R cells time-dependently. However, the extent of enhancement of u-PA and p38 MAPK expression in colo320 cells was much less than that in colo320/CCK2R cells. The gastrin antagonist L-365, 260 showed an effect of competitive inhibition on gastrin-induced u-PA expression and p38 kinase phosphorylation. The inhibitor SB203580 could sufficiently suppress gastrin-induced p38 kinase phosphorylation and significantly attenuate gastrin-induced u-PA mRNA and protein expressions in colo320/ CCK2 R cells in a dose-dependent manner.

CONCLUSION:

Gastrin-gastrin receptor signal transduction pathway can obviously induce u-PA expression in human colon cancer cells via activating the phosphorylation of p38 kinase.

• Authors: Mei Ming, Jie-ping Yu, Yan-hong Zhou, Jun Cao, Wen-chong Song, Hong-gang Yu, He-sheng Luo
• Journal: Zhonghua zhong liu za zhi [Chinese journal of oncology] (Zhonghua Zhong Liu Za Zhi) Vol. 29 Issue 1 Pg. 4-8 (Jan 2007) ISSN: 0253-3766 [Print] China
• PMID: 17575684 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzodiazepinones
• Gastrins
• Imidazoles
• Phenylurea Compounds
• Pyridines
• RNA, Messenger
• Receptor, Cholecystokinin B
• L 365260
• p38 Mitogen-Activated Protein Kinases
• Urokinase-Type Plasminogen Activator
• SB 203580

Topics

• Benzodiazepinones (pharmacology)
• Blotting, Western
• Cell Line, Tumor
• Colonic Neoplasms (genetics, metabolism, pathology)
• Gastrins (pharmacology)
• Gene Expression Regulation, Neoplastic (drug effects)
• Genetic Vectors
• Humans
• Imidazoles (pharmacology)
• Phenylurea Compounds (pharmacology)
• Phosphorylation (drug effects)
• Pyridines (pharmacology)
• RNA, Messenger (biosynthesis, genetics)
• Receptor, Cholecystokinin B (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction (drug effects)
• Transfection
• Urokinase-Type Plasminogen Activator (genetics, metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)