کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2023346 | 1542441 | 2007 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The CCK-2/gastrin splice variant receptor retaining intron 4 transactivates the COX-2 promoter in vitro
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
COXG-17COX-2PGE2Prostaglandins.CCKGPCRsCCAAT/enhancer-binding proteinsPGSPBGDC/EBPs - C / EBPG protein-coupled receptors - G گیرنده های پروتئینی همراهMAPK - MAPKcyclooxygenase - آنزیم سیکلواکسیژنازCyclooxygenase-2 - سیکلوکوکسیژناز2Hybridization probe - پروب هیبریداسیونmitogen-activated protein kinase - پروتئین کیناز فعال با mitogenProstaglandin E2 - پروستاگلاندین E2cholecystokinin - کولهسیستوکینینGastrin-17 - گاسترین 17
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: The CCK-2/gastrin splice variant receptor retaining intron 4 transactivates the COX-2 promoter in vitro The CCK-2/gastrin splice variant receptor retaining intron 4 transactivates the COX-2 promoter in vitro](/preview/png/2023346.png)
چکیده انگلیسی
The expression of the human cholecystokinin-2/gastrin receptor (CCK-2R) has been widely reported in human colorectal cancers. Recently, a splice variant of the CCK-2R retaining intron 4 (CCK-2i4svR) has been cloned from human colorectal cancers and postulated to exhibit constitutive activity. But its role in mediating carcinogenic effects of mature-amidated gastrin in colorectal cancers has not been fully explored. The purpose of the present study was to determine whether the activation of CCK-2i4svR by gastrin transactivates the COX-2 promoter in human colon cancer cells and in COS-7 cells. In this study, Colo320 cells and COS-7 cells were transfected with the human CCK-2R wild type (CCK-2wtR) (COS-7WT, Colo320WT) and the human CCK-2i4svR (COS-7SV, Colo320SV) cDNA. After stimulation with gastrin-17 (G-17), transactivation of the COX-2 promoter was determined by luciferase reporter gene assay. 5â²deletions of the COX-2 promoter were transfected into Colo320 cells to narrow down the minimally required regulatory element. Induction of COX-2 expression was further explored at the mRNA level using real time RT-PCR. The effects of CCK-2i4svR activation on phosphorylation of ERK1/2, p38MAPK and JNK were examined by using immunoblotting. Prostaglandin E2 (PGE2) secretion was measured by ELISA. Our results showed that gastrin transactivates the COX-2 promoter in both Colo320 cells and COS-7 cells expressing the CCK-2i4svR cDNA. Inhibition of p38MAPK pathway using specific inhibitor significantly blocked the gastrin-induced COX-2 transactivation. Gastrin time-dependently increased COX-2 mRNA expression, the peak mRNA levels appeared at 10Â h after stimulation. PGE2 secretion from gastrin-treated cells increased significantly 8Â h after stimulation. Treatment with gastrin also stimulated PGE2 secretion in the Colo320 cells expressing CCK-2i4svR. In conclusion, the CCK-2i4svR mediates transactivation of the COX-2 promoter and MAPK pathway is involved in this process.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Regulatory Peptides - Volume 144, Issues 1â3, 1 December 2007, Pages 34-42
Journal: Regulatory Peptides - Volume 144, Issues 1â3, 1 December 2007, Pages 34-42
نویسندگان
He Huang, Nikolaus Ansorge, Henning Schrader, Matthias Banasch, Hong-Gang Yu, Wolfgang E. Schmidt, Michael Höcker, Frank Schmitz,