Systemic analysis of gene expression profiles identifies ErbB3 as a potential drug target in pediatric alveolar rhabdomyosarcoma.

Pediatric sarcomas, including rhabdomyosarcomas, Ewing's sarcoma, and osteosarcoma, are aggressive tumors with poor survival rates. To overcome problems associated with nonselectivity of the current therapeutic approaches, targeted therapeutics have been developed. Currently, an increasing numb...

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Autores principales:	Janne Nordberg, John Patrick Mpindi, Kristiina Iljin, Arto Tapio Pulliainen, Markku Kallajoki, Olli Kallioniemi, Klaus Elenius, Varpu Elenius
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bb05e23f4e6d442f98e303fc92e8b5cc
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spelling	oai:doaj.org-article:bb05e23f4e6d442f98e303fc92e8b5cc2021-11-18T08:06:16ZSystemic analysis of gene expression profiles identifies ErbB3 as a potential drug target in pediatric alveolar rhabdomyosarcoma.1932-620310.1371/journal.pone.0050819https://doaj.org/article/bb05e23f4e6d442f98e303fc92e8b5cc2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23227212/?tool=EBIhttps://doaj.org/toc/1932-6203Pediatric sarcomas, including rhabdomyosarcomas, Ewing's sarcoma, and osteosarcoma, are aggressive tumors with poor survival rates. To overcome problems associated with nonselectivity of the current therapeutic approaches, targeted therapeutics have been developed. Currently, an increasing number of such drugs are used for treating malignancies of adult patients but little is known about their effects in pediatric patients. We analyzed expression of 24 clinically approved target genes in a wide variety of pediatric normal and malignant tissues using a novel high-throughput systems biology approach. Analysis of the Genesapiens database of human transcriptomes demonstrated statistically significant up-regulation of VEGFC and EPHA2 in Ewing's sarcoma, and ERBB3 in alveolar rhabdomyosarcomas. In silico data for ERBB3 was validated by demonstrating ErbB3 protein expression in pediatric rhabdomyosarcoma in vitro and in vivo. ERBB3 overexpression promoted whereas ERBB3-targeted siRNA suppressed rhabdomyosarcoma cell gowth, indicating a functional role for ErbB3 signaling in rhabdomyosarcoma. These data suggest that drugs targeting ErbB3, EphA2 or VEGF-C could be further tested as therapeutic targets for pediatric sarcomas.Janne NordbergJohn Patrick MpindiKristiina IljinArto Tapio PulliainenMarkku KallajokiOlli KallioniemiKlaus EleniusVarpu EleniusPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e50819 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Janne Nordberg John Patrick Mpindi Kristiina Iljin Arto Tapio Pulliainen Markku Kallajoki Olli Kallioniemi Klaus Elenius Varpu Elenius Systemic analysis of gene expression profiles identifies ErbB3 as a potential drug target in pediatric alveolar rhabdomyosarcoma.
description	Pediatric sarcomas, including rhabdomyosarcomas, Ewing's sarcoma, and osteosarcoma, are aggressive tumors with poor survival rates. To overcome problems associated with nonselectivity of the current therapeutic approaches, targeted therapeutics have been developed. Currently, an increasing number of such drugs are used for treating malignancies of adult patients but little is known about their effects in pediatric patients. We analyzed expression of 24 clinically approved target genes in a wide variety of pediatric normal and malignant tissues using a novel high-throughput systems biology approach. Analysis of the Genesapiens database of human transcriptomes demonstrated statistically significant up-regulation of VEGFC and EPHA2 in Ewing's sarcoma, and ERBB3 in alveolar rhabdomyosarcomas. In silico data for ERBB3 was validated by demonstrating ErbB3 protein expression in pediatric rhabdomyosarcoma in vitro and in vivo. ERBB3 overexpression promoted whereas ERBB3-targeted siRNA suppressed rhabdomyosarcoma cell gowth, indicating a functional role for ErbB3 signaling in rhabdomyosarcoma. These data suggest that drugs targeting ErbB3, EphA2 or VEGF-C could be further tested as therapeutic targets for pediatric sarcomas.
format	article
author	Janne Nordberg John Patrick Mpindi Kristiina Iljin Arto Tapio Pulliainen Markku Kallajoki Olli Kallioniemi Klaus Elenius Varpu Elenius
author_facet	Janne Nordberg John Patrick Mpindi Kristiina Iljin Arto Tapio Pulliainen Markku Kallajoki Olli Kallioniemi Klaus Elenius Varpu Elenius
author_sort	Janne Nordberg
title	Systemic analysis of gene expression profiles identifies ErbB3 as a potential drug target in pediatric alveolar rhabdomyosarcoma.
title_short	Systemic analysis of gene expression profiles identifies ErbB3 as a potential drug target in pediatric alveolar rhabdomyosarcoma.
title_full	Systemic analysis of gene expression profiles identifies ErbB3 as a potential drug target in pediatric alveolar rhabdomyosarcoma.
title_fullStr	Systemic analysis of gene expression profiles identifies ErbB3 as a potential drug target in pediatric alveolar rhabdomyosarcoma.
title_full_unstemmed	Systemic analysis of gene expression profiles identifies ErbB3 as a potential drug target in pediatric alveolar rhabdomyosarcoma.
title_sort	systemic analysis of gene expression profiles identifies erbb3 as a potential drug target in pediatric alveolar rhabdomyosarcoma.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/bb05e23f4e6d442f98e303fc92e8b5cc
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Systemic analysis of gene expression profiles identifies ErbB3 as a potential drug target in pediatric alveolar rhabdomyosarcoma.

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