کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2131708 | 1086655 | 2008 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Deletion of exon 8 increases cisplatin-induced E-cadherin cleavage
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کلمات کلیدی
MDACTLPI3-kinaseDAPIAEC4,6-diamidino-2-phenylindole - 4،6-دیامیدین-2-فنیلینولAkt/Protein kinase B - Akt / Protein Kinase BDMSO - DMSOE-cadherin - E-CadherinAkt/PKB - آکت / PKBstandard deviation - انحراف معیارCleavage - انهدامRoom temperature - دمای اتاقDimethyl sulfoxide - دیمتیل سولفواکسیدcisplatin - سیس پلاتینfull length - طول کاملPhosphatidylinositol 3-kinase - فسفاتیدیلینواستیل 3-کینازwild-type - نوع وحشیControl - کنترل
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Deletion of exon 8 increases cisplatin-induced E-cadherin cleavage Deletion of exon 8 increases cisplatin-induced E-cadherin cleavage](/preview/png/2131708.png)
چکیده انگلیسی
E-Cadherin-mediated cell-cell adhesion plays a key role in epithelial cell survival and loss of E-cadherin or β-catenin expression is associated with invasive tumor growth. Somatic E-cadherin mutations have been identified in sporadic diffuse-type gastric carcinoma. Here, we analysed the fate of E-cadherin with an in frame deletion of exon 8 compared to wild-type E-cadherin and the involved signalling events during cisplatin-induced apoptosis. We report that mutant E-cadherin was more readily cleaved during apoptosis than the wild-type form. Also β-catenin, an important binding partner of E-cadherin, was processed. E-cadherin cleavage resulted in disconnection of the actin cytoskeleton and accumulation of E-cadherin and β-catenin in the cytoplasm. Inhibitor studies demonstrated that E-cadherin cleavage was caused by a caspase-3-mediated mechanism. We identified the Akt/PKB and the ERK1/2 signalling pathways as important regulators since inhibition resulted in increased E-cadherin cleavage and apoptosis. In summary, we clearly demonstrate that somatic E-cadherin mutations affect apoptosis regulation in that way that they can facilitate the disruption of adherens junctions thereby possibly influencing the response to cisplatin-based chemotherapy. Elucidating the mechanisms that regulate the apoptotic program of tumor cells can contribute to a better understanding of tumor development and potentially be relevant for therapeutic drug design.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 314, Issue 1, 1 January 2008, Pages 153-163
Journal: Experimental Cell Research - Volume 314, Issue 1, 1 January 2008, Pages 153-163
نویسندگان
Margit Fuchs, Christine Hermannstädter, Peter Hutzler, Georg Häcker, Ferdinand Haller, Heinz Höfler, Birgit Luber,