Cholecystokinin-2 Receptor Modulates Cell Adhesion Through Beta 1-integrin in Human Pancreatic Cancer Cells.
From: INSERM U 531, IFR 31, Institut Louis Bugnard, Toulouse, France.
Oncogene
- Publish Date: Jul 2006
- ISSN: 0950-9232
- Volume: 25
- Issue: 32
- Pages: 4421-8
- Medium: Print
- Language: English
- Citation (JAMA): Cayrol C, Clerc P, Bertrand C, et al. Cholecystokinin-2 Receptor Modulates Cell Adhesion Through Beta 1-integrin in Human Pancreatic Cancer Cells.. Oncogene Jul 2006;25:4421-8
Abstract
Several lines of evidence suggest that gastrin and the CCK-2 receptor (CCK2R) could contribute to pancreatic carcinogenesis by modulating processes such as proliferation, cell adhesion or migration. In the current study, we used a ‘cancer gene array’ and identified beta1-integrin subunit as a new gastrin-regulated gene in human pancreatic cancer cells. We also demonstrated that Src family kinases and the phosphatidylinositol-3-kinase (PI-3-kinase) pathway play a crucial role in the expression of beta1-integrin induced by gastrin. Our results also showed that gastrin modulates cell-substrate adhesion via beta1-integrin. Indeed, using blocking anti-beta1-integrin monoclonal antibodies, we completely reversed the increase in cell-substrate adhesion induced by gastrin. In addition, we observed that in response to gastrin, beta1-integrin is tyrosine phosphorylated by Src family kinases and associates with paxillin, a scaffold protein involved in focal adhesion and integrin signalling. This mechanism might be involved in gastrin-induced cell adhesion. Moreover, we showed in vivo that targeted CCK2R expression in the pancreas of Elas-CCK2 mice leads to the overexpression of beta1-integrin. This process may contribute to pancreatic tumour development observed in these transgenic animals.
Mesh Headings (Keywords): Animals, Antigens, CD29, Cell Adhesion, Cell Line, Tumor, Gastrins, Humans, Mice, Mice, Inbred C57BL, Mice, Transgenic, Pancreatic Neoplasms, Receptor, Cholecystokinin B
Check for Full Text / PubMed Unique Identifier (PMID): 16547500
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