مورد إلكتروني
Activation of ERBB4 in glioblastoma can contribute to increased tumorigenicity and influence therapeutic response.
| العنوان: | Activation of ERBB4 in glioblastoma can contribute to increased tumorigenicity and influence therapeutic response. |
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| بيانات النشر: | MDPI AG (Postfach, Basel CH-4005, Switzerland) Switzerland 2018-08-16 |
| تفاصيل مُضافة: | Mischel P.S. Greenall S.A. Longano A.B. Gottardo N.G. Wang R. Tabar V. Adams T.E. Johns T.G. Donoghue J.F. Kerr L.T. Alexander N.W. |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Glioblastoma (GBM) is often resistant to conventional and targeted therapeutics. ErbB2 Receptor Tyrosine Kinase 4 (ERBB4) is expressed throughout normal brain and is an oncogene in several pediatric brain cancers; therefore, we investigated ERBB4 as a prognostic marker and therapeutic target in GBM. Using RT-qPCR, we quantified mRNA encoding total ERBB4 and known ERBB4 variants in GBM and non-neoplastic normal brain (NNB) samples. Using immunohistochemistry, we characterized the localization of total and phosphorylated ERBB4 (p-ERBB4) and EGFR protein in archived GBM samples and assessed their association with patient survival. Furthermore, we evaluated the effect of ERBB4 phosphorylation on angiogenesis and tumorigenicity in GBM xenograft models. Total ERBB4 mRNA was significantly lower in GBM than NNB samples, with the juxtamembrane JM-a and cytoplasmic CYT-2 variants predominating. ERBB4 protein was ubiquitously expressed in GBM but was not associated with patient survival. However, high p-ERBB4 in 11% of archived GBM samples, independent of p-EGFR, was associated with shorter patient survival (12.0 +/- 3.2 months) than was no p-ERBB4 (22.5 +/- 9.5 months). Increased ERBB4 activation was also associated with increased proliferation, angiogenesis, tumorigenicity and reduced sensitivity to anti-EGFR treatment in xenograft models. Despite low ERBB4 mRNA in GBM, the functional effects of increased ERBB4 activation identify ERBB4 as a potential prognostic and therapeutic target.Copyright © 2018 by the authors. Licensee MDPI, Basel, Switzerland. |
| مصطلحات الفهرس: | protein cleavage, protein expression, protein function, protein interaction, protein localization, protein phosphorylation, survival rate, upregulation, dacomitinib/dt [Drug Therapy], epidermal growth factor receptor 4/ec [Endogenous Compound], messenger RNA/ec [Endogenous Compound], panitumumab, carcinogenicity, angiogenesis, animal cell, animal experiment, animal model, article, cancer prognosis, cancer survival, cell activation, cell count, cell growth, cell proliferation, concentration response, cross reaction, disease marker, drug efficacy, drug response, drug tolerability, glioblastoma/dt [Drug Therapy], glioblastoma/et [Etiology], mouse, nerve cell, nonhuman, overall survival, Article |
| URL: | Cancers Click here for full text options LibKey Link |
| الإتاحة: | Open access content. Open access content Copyright 2018 Elsevier B.V., All rights reserved. |
| أرقام أخرى: | AUSHL oai:repository.monashhealth.org:1/37600 Cancers. 10 (8) (no pagination), 2018. Article Number: 243. Date of Publication: August 2018. 2072-6694 (electronic) https://repository.monashhealth.org/monashhealthjspui/handle/1/37600 623283559 (Donoghue, Kerr, Greenall, Johns) Oncogenic Signalling Group, Hudson Institute of Medical Research, 21-37 Wright Street, Clayton, VIC 3168, Australia (Kerr, Greenall, Johns) Department of Molecular and Translational Science, Monash University, Clayton, VIC 3168, Australia (Alexander, Gottardo, Johns) Telethon Kids Cancer Centre, Telethon Kids Institute, University of Western Australia, Perth, WA 6008, Australia (Longano) Department of Anatomical Pathology, Monash Medical Centre, Clayton, VIC 3168, Australia (Wang, Tabar) Department of Neurosurgery and Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States (Adams) Biomedical Manufacturing, Commonwealth Scientific and Industrial Research Organisation (CSIRO), Parkville, VIC 3052, Australia (Mischel) Ludwig Institute for Cancer Research, University of California San Diego, La Jolla, CA 92093, United States Donoghue J.F.; jacqueline.donoghue@unimelb.edu.au Kerr L.T.; Lauren.Kerr@cancer.org.uk Greenall S.A.; sameer.greenall@hudson.org.au Alexander N.W.; naomi.alexander@telethonkids.org.au Gottardo N.G.; Nicholas.Gottardo@telethonkids.org.au Johns T.G.; Terrance.Johns@telethonkids.org.au Longano A.B.; anthony.longano@monashhealth.org Wang R.; wangr@mskcc.org Tabar V.; tabarv@mskcc.org Adams T.E.; Tim.Adams@csiro.au Mischel P.S.; pmischel@ucsd.edu 1305107284 |
| المصدر المساهم: | MONASH HEALTH LIBRS From OAIster®, provided by the OCLC Cooperative. |
| رقم الأكسشن: | edsoai.on1305107284 |
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