Retinoblastoma treatment: impact of the glycolytic inhibitor 2-deoxy-d-glucose on molecular genomics expression in LHBETATAG retinal tumors

Yolanda Pi&ntilde;a,1 Samuel K Houston,1 Timothy G Murray,1 Tulay Koru-Sengul,2,3 Christina Decatur,1 William K Scott,4 Lubov Nathanson,4 Jennifer Clarke,2 Theodore J Lampidis,51Bascom Palmer Eye Institute, 2Department of Epidemiology and Public Health, 3Sylvester Comprehensive Cancer Center...

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Autores principales:	Pi&ntilde;a Y, Houston SK, Murray TG, Koru-Sengul T, Decatur C, Scott WK, Nathanson L, Clarke J, Lampidis TJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Ophthalmology RE1-994
Acceso en línea:	https://doaj.org/article/1046816bca3e4ac9a742a1934c9bb645
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spelling	oai:doaj.org-article:1046816bca3e4ac9a742a1934c9bb6452021-12-02T01:28:23ZRetinoblastoma treatment: impact of the glycolytic inhibitor 2-deoxy-d-glucose on molecular genomics expression in LHBETATAG retinal tumors1177-54671177-5483https://doaj.org/article/1046816bca3e4ac9a742a1934c9bb6452012-05-01T00:00:00Zhttp://www.dovepress.com/retinoblastoma-treatment-impact-of-the-glycolytic-inhibitor-2-deoxy-d--a9995https://doaj.org/toc/1177-5467https://doaj.org/toc/1177-5483Yolanda Pi&ntilde;a,1 Samuel K Houston,1 Timothy G Murray,1 Tulay Koru-Sengul,2,3 Christina Decatur,1 William K Scott,4 Lubov Nathanson,4 Jennifer Clarke,2 Theodore J Lampidis,51Bascom Palmer Eye Institute, 2Department of Epidemiology and Public Health, 3Sylvester Comprehensive Cancer Center, 4Department of Molecular Genomics, 5Department of Cell Biology and Anatomy, University of Miami Miller School of Medicine, Miami, FL, USAPurpose: The purpose of this study was to evaluate the effect of 2-deoxy-D-glucose (2-DG) on the spatial distribution of the genetic expression of key elements involved in angiogenesis, hypoxia, cellular metabolism, and apoptosis in LHBETATAG retinal tumors.Methods: The right eye of each LHBETATAG transgenic mouse (n = 24) was treated with either two or six subconjunctival injections of 2-DG (500 mg/kg) or saline control at 16 weeks of age. A gene expression array analysis was performed on five different intratumoral regions (apex, center, base, anterior-lateral, and posterior-lateral) using Affymetrix GeneChip Mouse Gene 1.0 ST arrays. To test for treatment effects of each probe within each region, a two-way analysis of variance was used.Results: Significant differences between treatment groups (ie, 0, 2, and 6 injections) were found as well as differences among the five retinal tumor regions evaluated (P &lt; 0.01). More than 100 genes were observed to be dysregulated by &ge;2-fold difference in expression between the three treatment groups, and their dysregulation varied across the five regions assayed. Several genes involved in pathways important for tumor cell growth (ie, angiogenesis, hypoxia, cellular metabolism, and apoptosis) were identified.Conclusions: 2-DG was found to significantly alter the gene expression in LHBETATAG retinal tumor cells according to their location within the tumor as well as the treatment schedule. 2-DG&#39;s effects on genetic expression found here correlate with previous reported results on varied processes involved in its in vitro and in vivo activity in inhibiting tumor cell growth.Keywords: retinoblastoma, hypoxia, genetic expression, glycolytic inhibitor, 2-DGPi&ntilde;a YHouston SKMurray TGKoru-Sengul TDecatur CScott WKNathanson LClarke JLampidis TJDove Medical PressarticleOphthalmologyRE1-994ENClinical Ophthalmology, Vol 2012, Iss default, Pp 817-830 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Ophthalmology RE1-994
spellingShingle	Ophthalmology RE1-994 Pi&ntilde;a Y Houston SK Murray TG Koru-Sengul T Decatur C Scott WK Nathanson L Clarke J Lampidis TJ Retinoblastoma treatment: impact of the glycolytic inhibitor 2-deoxy-d-glucose on molecular genomics expression in LHBETATAG retinal tumors
description	Yolanda Pi&ntilde;a,1 Samuel K Houston,1 Timothy G Murray,1 Tulay Koru-Sengul,2,3 Christina Decatur,1 William K Scott,4 Lubov Nathanson,4 Jennifer Clarke,2 Theodore J Lampidis,51Bascom Palmer Eye Institute, 2Department of Epidemiology and Public Health, 3Sylvester Comprehensive Cancer Center, 4Department of Molecular Genomics, 5Department of Cell Biology and Anatomy, University of Miami Miller School of Medicine, Miami, FL, USAPurpose: The purpose of this study was to evaluate the effect of 2-deoxy-D-glucose (2-DG) on the spatial distribution of the genetic expression of key elements involved in angiogenesis, hypoxia, cellular metabolism, and apoptosis in LHBETATAG retinal tumors.Methods: The right eye of each LHBETATAG transgenic mouse (n = 24) was treated with either two or six subconjunctival injections of 2-DG (500 mg/kg) or saline control at 16 weeks of age. A gene expression array analysis was performed on five different intratumoral regions (apex, center, base, anterior-lateral, and posterior-lateral) using Affymetrix GeneChip Mouse Gene 1.0 ST arrays. To test for treatment effects of each probe within each region, a two-way analysis of variance was used.Results: Significant differences between treatment groups (ie, 0, 2, and 6 injections) were found as well as differences among the five retinal tumor regions evaluated (P &lt; 0.01). More than 100 genes were observed to be dysregulated by &ge;2-fold difference in expression between the three treatment groups, and their dysregulation varied across the five regions assayed. Several genes involved in pathways important for tumor cell growth (ie, angiogenesis, hypoxia, cellular metabolism, and apoptosis) were identified.Conclusions: 2-DG was found to significantly alter the gene expression in LHBETATAG retinal tumor cells according to their location within the tumor as well as the treatment schedule. 2-DG&#39;s effects on genetic expression found here correlate with previous reported results on varied processes involved in its in vitro and in vivo activity in inhibiting tumor cell growth.Keywords: retinoblastoma, hypoxia, genetic expression, glycolytic inhibitor, 2-DG
format	article
author	Pi&ntilde;a Y Houston SK Murray TG Koru-Sengul T Decatur C Scott WK Nathanson L Clarke J Lampidis TJ
author_facet	Pi&ntilde;a Y Houston SK Murray TG Koru-Sengul T Decatur C Scott WK Nathanson L Clarke J Lampidis TJ
author_sort	Pi&ntilde;a Y
title	Retinoblastoma treatment: impact of the glycolytic inhibitor 2-deoxy-d-glucose on molecular genomics expression in LHBETATAG retinal tumors
title_short	Retinoblastoma treatment: impact of the glycolytic inhibitor 2-deoxy-d-glucose on molecular genomics expression in LHBETATAG retinal tumors
title_full	Retinoblastoma treatment: impact of the glycolytic inhibitor 2-deoxy-d-glucose on molecular genomics expression in LHBETATAG retinal tumors
title_fullStr	Retinoblastoma treatment: impact of the glycolytic inhibitor 2-deoxy-d-glucose on molecular genomics expression in LHBETATAG retinal tumors
title_full_unstemmed	Retinoblastoma treatment: impact of the glycolytic inhibitor 2-deoxy-d-glucose on molecular genomics expression in LHBETATAG retinal tumors
title_sort	retinoblastoma treatment: impact of the glycolytic inhibitor 2-deoxy-d-glucose on molecular genomics expression in lhbetatag retinal tumors
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/1046816bca3e4ac9a742a1934c9bb645
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Retinoblastoma treatment: impact of the glycolytic inhibitor 2-deoxy-d-glucose on molecular genomics expression in LHBETATAG retinal tumors

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