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Expression of the RNA Helicase DDX3 and the Hypoxia Response in Breast Cancer
- Source :
- PLoS ONE, Vol 8, Iss 5, p e63548 (2013), PLoS ONE
- Publication Year :
- 2013
- Publisher :
- Public Library of Science (PLoS), 2013.
-
Abstract
- AimsDDX3 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.Methods and resultsDDX3 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.ConclusionsIn 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.
- Subjects :
- Male
Receptor, ErbB-2
Tumor Physiology
Gene Expression
Cell Cycle Proteins
medicine.disease_cause
DEAD-box RNA Helicases
Oxidative Damage
Molecular Cell Biology
Basic Cancer Research
Breast Tumors
Pathology
Transcriptional regulation
Receptor, Notch1
Hypoxia
Cellular Stress Responses
Aged, 80 and over
Multidisciplinary
Kinase
Forkhead Transcription Factors
Middle Aged
Immunohistochemistry
RNA Helicase A
ErbB Receptors
Gene Expression Regulation, Neoplastic
Oncology
Medicine
Female
Molecular Pathology
Research Article
Signal Transduction
Adult
Histology
Proto-Oncogene Proteins c-akt
Science
Breast Neoplasms
Transferrin receptor
In Vitro Techniques
Biology
Breast cancer
Diagnostic Medicine
medicine
Humans
Transcription factor
Adaptor Proteins, Signal Transducing
Aged
Cancers and Neoplasms
Hypoxia-Inducible Factor 1, alpha Subunit
medicine.disease
Molecular biology
Cancer research
Carcinogenesis
Biomarkers
Transcription Factors
General Pathology
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....1bd3e86bd79264c129fa869b02309d52