αV integrin:A new gastrin target in human pancreatic cancer cells

查看全文 作　　者：Celine [1]Cayrol;Claudine [1]Bertrand;Aline Kowalski-[1]Chauvel;Laurence [2]Daulhac;Elizabeth Cohen-Jonathan-[1]Moyal;Audrey [1]Ferrand;Catherine [1]Seva

机构地区：[1]INSERM UMR1037-Cancer Research Center of Toulouse Paul Sabatier University Toulouse Ⅲ,31432 Toulouse cedex 4 France;[2]INSERM U766 Department of pharma-cology Clermont 1 University of Pharmacy,63001 Clermont-Ferrand France

出　　处：《World Journal of Gastroenterology》索引2011年第17卷第40期,共8页

基　　金：Supported by Grants from INSERM 摘　　要：AIM:To analyse αV integrin expression induced by gas-trin in pancreatic cancer models. METHODS:αV integrin mRNA expression in human pan-creatic cancer cells was analysed using a 'cancer genes' array and confirmed by real-time reverse transcription-polymerase chain reaction (PCR). Western blotting and semi-quantitative immunohistochemistry were used to examine protein levels in human pancreatic cancer cell lines and pancreatic tissues, respectively. The role of αV integrin on gastrin-induced cell adhesion was examined using blocking anti-αV integrin monoclonal antibodies. Adherent cells were quantified by staining with crystal violet.RESULTS: Using a 'cancer genes' array we identified αV integrin as a new gastrin target gene in human pancreatic cancer cells. A quantitative real-time PCR approach was used to confirm αV integrin gene expression. We also demonstrate that Src family kinases and the PI 3-kinase, two signalling pathways specifically activated by the CCK-2 receptor (CCK2R), are involved in gastrin-mediated αV integrin expression. In contrast, inhibition of the ERK pathway was without any effect on αV integrin expression induced by gastrin. Our results also show that gastrin modulates cell adhesion via α V integrins. Indeed, in vitro adhesion assays performed on fibronectin show that gastrin significantly increases adhesion of pancreatic cancer cells. The use of blocking anti-αV integrin monoclonal antibodies completely reversed the increase in cell-substrate adhesion induced by gastrin. In addition, we showed in vivo that the targeted CCK2R expression in the pancreas of Elas-CCK2 mice, leads to the overexpression of αV integrin. This process may contribute to pancreatic tumour development observed in these transgenic animals. CONCLUSION:αV integrin is a new gastrin target in pancreatic cancer models and contributes to gastrin effects on cell adhesion. 关键词：胃泌素胰腺癌癌细胞整合人类 WESTERN印迹细胞粘附单克隆抗体

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αV integrin:A new gastrin target in human pancreatic cancer cells

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