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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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0063548&type=printable |
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| 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 |
| collection | DOAJ |
| 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 |
| id | doaj-art-fcc986e1b2e342c79b60d68671d86112 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-fcc986e1b2e342c79b60d68671d861122025-08-20T02:30:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0185e6354810.1371/journal.pone.0063548Expression of the RNA helicase DDX3 and the hypoxia response in breast cancer.Guus M BolVenu RamanPetra van der GroepJeroen F VermeulenArvind H PatelElsken van der WallPaul J van Diest<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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0063548&type=printable |
| spellingShingle | 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. PLoS ONE |
| title | 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_short | 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 |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0063548&type=printable |
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