کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2151457 | 1089994 | 2012 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Activation of Multiple ERBB Family Receptors Mediates Glioblastoma Cancer Stem-like Cell Resistance to EGFR-Targeted Inhibition
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
EGFRCSCEGFRTKNSCGFAPbFGFTKIGBMDAPI4′,6-diamidino-2-phenylindole - 4 '، 6-دیامیدینو-2-فنیلینولMRI - امآرآی یا تصویرسازی تشدید مغناطیسیMagnetic resonance imaging - تصویربرداری رزونانس مغناطیسیRTK, Receptor tyrosine kinase - تیروزین کینازهای گیرنده ایCancer stem-like cell - سلول بنیادی سرطانیNeural stem cell - سلول های بنیادی عصبیepidermal growth factor - عامل رشد اپیدرمیbasic fibroblast growth factor - فاکتور رشد فیبروبلاست پایهTyrosine kinase inhibitor - مهار کننده تیروزین کینازGlial fibrillary acidic protein - پروتئین اسیدی فیبریلاسیون گلایالGlioblastoma multiforme - گلیوبلاستوم مولتیفرم، گلیوبلاستوماEpidermal growth factor receptor - گیرنده فاکتور رشد اپیدرمال
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Activation of Multiple ERBB Family Receptors Mediates Glioblastoma Cancer Stem-like Cell Resistance to EGFR-Targeted Inhibition Activation of Multiple ERBB Family Receptors Mediates Glioblastoma Cancer Stem-like Cell Resistance to EGFR-Targeted Inhibition](/preview/png/2151457.png)
چکیده انگلیسی
Epidermal growth factor receptor (EGFR) signaling is strongly implicated in glioblastoma (GBM) tumorigenesis. However, molecular agents targeting EGFR have demonstrated minimal efficacy in clinical trials, suggesting the existence of GBM resistance mechanisms. GBM cells with stem-like properties (CSCs) are highly efficient at tumor initiation and exhibit therapeutic resistance. In this study, GBMCSC lines showed sphere-forming and tumor initiation capacity after EGF withdrawal from cell culture media, compared with normal neural stem cells that rapidly perished after EGF withdrawal. Compensatory activation of related ERBB family receptors (ERBB2 and ERBB3) was observed in GBM CSCs deprived of EGFR signal (EGF deprivation or cetuximab inhibition), suggesting an intrinsic GBM resistance mechanism for EGFR-targeted therapy. Dual inhibition of EGFR and ERBB2 with lapatinib significantly reduced GBM proliferation in colony formation assays compared to cetuximab-mediated EGFR-specific inhibition. Phosphorylation of downstream ERBB signaling components (AKT, ERK1/2) and GBM CSC proliferation were inhibited by lapatinib. Collectively, these findings show that GBM therapeutic resistance to EGFR inhibitors may be explained by compensatory activation of EGFR-related family members (ERBB2, ERBB3) enabling GBM CSC proliferation, and therefore simultaneous blockade of multiple ERBB family members may be required for more efficacious GBM therapy.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neoplasia - Volume 14, Issue 5, May 2012, Pages 420-428, IN11-IN13
Journal: Neoplasia - Volume 14, Issue 5, May 2012, Pages 420-428, IN11-IN13
نویسندگان
Paul A. Clark, Mari Iida, Daniel M. Treisman, Haviryaji Kalluri, Sathyapriya Ezhilan, Michael Zorniak, Deric L. Wheeler, John S. Kuo,