EGFR and PDGFRA co-expression and heterodimerization in glioblastoma tumor sphere lines

Abstract Concurrent amplifications of EGFR and PDGFRA have been reported in up to 5% of glioblastoma (GBM) and it remains unclear why such independent amplification events, and associated receptor overexpression, would be adaptive during glioma evolution. Here, we document that EGFR and PDGFRA prote...

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Autores principales:	Debyani Chakravarty, Alicia M. Pedraza, Jesse Cotari, Angela H. Liu, Diana Punko, Aushim Kokroo, Jason T. Huse, Gregoire Altan-Bonnet, Cameron W. Brennan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/052b404398294acfaa36d10454862c2e
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spelling	oai:doaj.org-article:052b404398294acfaa36d10454862c2e2021-12-02T11:40:57ZEGFR and PDGFRA co-expression and heterodimerization in glioblastoma tumor sphere lines10.1038/s41598-017-08940-92045-2322https://doaj.org/article/052b404398294acfaa36d10454862c2e2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08940-9https://doaj.org/toc/2045-2322Abstract Concurrent amplifications of EGFR and PDGFRA have been reported in up to 5% of glioblastoma (GBM) and it remains unclear why such independent amplification events, and associated receptor overexpression, would be adaptive during glioma evolution. Here, we document that EGFR and PDGFRA protein co-expression occurs in 37% of GBM. There is wide cell-to-cell variation in the expressions of these receptor tyrosine kinases (RTKs) in stable tumor sphere lines, frequently defining tumor cell subpopulations with distinct sensitivities to growth factors and RTK inhibitors. We also find evidence for functional transactivation of PDGFRA by EGFR and EGF-induced receptor heterodimerization, both of which are abolished by EGFR inhibitors. These results indicate that GBM growth responses to targeted therapies previously tested in clinical trials are strongly influenced by the balance of EGFR and PDGFRA activation in individual cells, which is heterogeneous at baseline.Debyani ChakravartyAlicia M. PedrazaJesse CotariAngela H. LiuDiana PunkoAushim KokrooJason T. HuseGregoire Altan-BonnetCameron W. BrennanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Debyani Chakravarty Alicia M. Pedraza Jesse Cotari Angela H. Liu Diana Punko Aushim Kokroo Jason T. Huse Gregoire Altan-Bonnet Cameron W. Brennan EGFR and PDGFRA co-expression and heterodimerization in glioblastoma tumor sphere lines
description	Abstract Concurrent amplifications of EGFR and PDGFRA have been reported in up to 5% of glioblastoma (GBM) and it remains unclear why such independent amplification events, and associated receptor overexpression, would be adaptive during glioma evolution. Here, we document that EGFR and PDGFRA protein co-expression occurs in 37% of GBM. There is wide cell-to-cell variation in the expressions of these receptor tyrosine kinases (RTKs) in stable tumor sphere lines, frequently defining tumor cell subpopulations with distinct sensitivities to growth factors and RTK inhibitors. We also find evidence for functional transactivation of PDGFRA by EGFR and EGF-induced receptor heterodimerization, both of which are abolished by EGFR inhibitors. These results indicate that GBM growth responses to targeted therapies previously tested in clinical trials are strongly influenced by the balance of EGFR and PDGFRA activation in individual cells, which is heterogeneous at baseline.
format	article
author	Debyani Chakravarty Alicia M. Pedraza Jesse Cotari Angela H. Liu Diana Punko Aushim Kokroo Jason T. Huse Gregoire Altan-Bonnet Cameron W. Brennan
author_facet	Debyani Chakravarty Alicia M. Pedraza Jesse Cotari Angela H. Liu Diana Punko Aushim Kokroo Jason T. Huse Gregoire Altan-Bonnet Cameron W. Brennan
author_sort	Debyani Chakravarty
title	EGFR and PDGFRA co-expression and heterodimerization in glioblastoma tumor sphere lines
title_short	EGFR and PDGFRA co-expression and heterodimerization in glioblastoma tumor sphere lines
title_full	EGFR and PDGFRA co-expression and heterodimerization in glioblastoma tumor sphere lines
title_fullStr	EGFR and PDGFRA co-expression and heterodimerization in glioblastoma tumor sphere lines
title_full_unstemmed	EGFR and PDGFRA co-expression and heterodimerization in glioblastoma tumor sphere lines
title_sort	egfr and pdgfra co-expression and heterodimerization in glioblastoma tumor sphere lines
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/052b404398294acfaa36d10454862c2e
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EGFR and PDGFRA co-expression and heterodimerization in glioblastoma tumor sphere lines

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