Expression of the RNA helicase DDX3 and the hypoxia response in breast cancer.

<h4>Aims</h4>DDX3 is an RNA helicase that has antiapoptotic properties, and promotes proliferation and transformation. In addition, DDX3 was shown to be a direct downstream target of HIF-1α (the master regulatory of the hypoxia response) in breast cancer cell lines. However, the relation...

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Autores principales:	Guus M Bol, Venu Raman, Petra van der Groep, Jeroen F Vermeulen, Arvind H Patel, Elsken van der Wall, Paul J van Diest
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fcc986e1b2e342c79b60d68671d86112
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spelling	oai:doaj.org-article:fcc986e1b2e342c79b60d68671d861122021-11-18T07:45:29ZExpression of the RNA helicase DDX3 and the hypoxia response in breast cancer.1932-620310.1371/journal.pone.0063548https://doaj.org/article/fcc986e1b2e342c79b60d68671d861122013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23696831/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Aims</h4>DDX3 is an RNA helicase that has antiapoptotic properties, and promotes proliferation and transformation. In addition, DDX3 was shown to be a direct downstream target of HIF-1α (the master regulatory of the hypoxia response) in breast cancer cell lines. However, the relation between DDX3 and hypoxia has not been addressed in human tumors. In this paper, we studied the relation between DDX3 and the hypoxic responsive proteins in human breast cancer.<h4>Methods and results</h4>DDX3 expression was investigated by immunohistochemistry in breast cancer in comparison with hypoxia related proteins HIF-1α, GLUT1, CAIX, EGFR, HER2, Akt1, FOXO4, p53, ERα, COMMD1, FER kinase, PIN1, E-cadherin, p21, p27, Transferrin receptor, FOXO3A, c-Met and Notch1. DDX3 was overexpressed in 127 of 366 breast cancer patients, and was correlated with overexpression of HIF-1α and its downstream genes CAIX and GLUT1. Moreover, DDX3 expression correlated with hypoxia-related proteins EGFR, HER2, FOXO4, ERα and c-Met in a HIF-1α dependent fashion, and with COMMD1, FER kinase, Akt1, E-cadherin, TfR and FOXO3A independent of HIF-1α.<h4>Conclusions</h4>In invasive breast cancer, expression of DDX3 was correlated with overexpression of HIF-1α and many other hypoxia related proteins, pointing to a distinct role for DDX3 under hypoxic conditions and supporting the oncogenic role of DDX3 which could have clinical implication for current development of DDX3 inhibitors.Guus M BolVenu RamanPetra van der GroepJeroen F VermeulenArvind H PatelElsken van der WallPaul J van DiestPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 5, p e63548 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Guus M Bol Venu Raman Petra van der Groep Jeroen F Vermeulen Arvind H Patel Elsken van der Wall Paul J van Diest Expression of the RNA helicase DDX3 and the hypoxia response in breast cancer.
description	<h4>Aims</h4>DDX3 is an RNA helicase that has antiapoptotic properties, and promotes proliferation and transformation. In addition, DDX3 was shown to be a direct downstream target of HIF-1α (the master regulatory of the hypoxia response) in breast cancer cell lines. However, the relation between DDX3 and hypoxia has not been addressed in human tumors. In this paper, we studied the relation between DDX3 and the hypoxic responsive proteins in human breast cancer.<h4>Methods and results</h4>DDX3 expression was investigated by immunohistochemistry in breast cancer in comparison with hypoxia related proteins HIF-1α, GLUT1, CAIX, EGFR, HER2, Akt1, FOXO4, p53, ERα, COMMD1, FER kinase, PIN1, E-cadherin, p21, p27, Transferrin receptor, FOXO3A, c-Met and Notch1. DDX3 was overexpressed in 127 of 366 breast cancer patients, and was correlated with overexpression of HIF-1α and its downstream genes CAIX and GLUT1. Moreover, DDX3 expression correlated with hypoxia-related proteins EGFR, HER2, FOXO4, ERα and c-Met in a HIF-1α dependent fashion, and with COMMD1, FER kinase, Akt1, E-cadherin, TfR and FOXO3A independent of HIF-1α.<h4>Conclusions</h4>In invasive breast cancer, expression of DDX3 was correlated with overexpression of HIF-1α and many other hypoxia related proteins, pointing to a distinct role for DDX3 under hypoxic conditions and supporting the oncogenic role of DDX3 which could have clinical implication for current development of DDX3 inhibitors.
format	article
author	Guus M Bol Venu Raman Petra van der Groep Jeroen F Vermeulen Arvind H Patel Elsken van der Wall Paul J van Diest
author_facet	Guus M Bol Venu Raman Petra van der Groep Jeroen F Vermeulen Arvind H Patel Elsken van der Wall Paul J van Diest
author_sort	Guus M Bol
title	Expression of the RNA helicase DDX3 and the hypoxia response in breast cancer.
title_short	Expression of the RNA helicase DDX3 and the hypoxia response in breast cancer.
title_full	Expression of the RNA helicase DDX3 and the hypoxia response in breast cancer.
title_fullStr	Expression of the RNA helicase DDX3 and the hypoxia response in breast cancer.
title_full_unstemmed	Expression of the RNA helicase DDX3 and the hypoxia response in breast cancer.
title_sort	expression of the rna helicase ddx3 and the hypoxia response in breast cancer.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/fcc986e1b2e342c79b60d68671d86112
work_keys_str_mv	AT guusmbol expressionofthernahelicaseddx3andthehypoxiaresponseinbreastcancer AT venuraman expressionofthernahelicaseddx3andthehypoxiaresponseinbreastcancer AT petravandergroep expressionofthernahelicaseddx3andthehypoxiaresponseinbreastcancer AT jeroenfvermeulen expressionofthernahelicaseddx3andthehypoxiaresponseinbreastcancer AT arvindhpatel expressionofthernahelicaseddx3andthehypoxiaresponseinbreastcancer AT elskenvanderwall expressionofthernahelicaseddx3andthehypoxiaresponseinbreastcancer AT pauljvandiest expressionofthernahelicaseddx3andthehypoxiaresponseinbreastcancer
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Expression of the RNA helicase DDX3 and the hypoxia response in breast cancer.

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