Document Detail


Genome-wide expression analysis using microarray identified complex signaling pathways modulated by hypoxia in nasopharyngeal carcinoma.
MedLine Citation:
PMID:  17320280     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Previously, we showed that hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha, carbonic anhydrase IX (CA IX), and vascular endothelial growth factor (VEGF) were frequently coexpressed in tumor biopsies from patients of nasopharyngeal carcinoma (NPC) and were associated with poor outcome after radiotherapy. Here, we further studied hypoxic induction of HIF-1alpha, HIF-2alpha, CA IX, and VEGF in NPC cell lines, investigated hypoxia-modulated gene expression in NPC cell lines by Affymetrix GeneChip Array expression profiling, and identified pathways influenced by hypoxia and novel genes not previously recognized as hypoxia-inducible. Differentially regulated genes under hypoxia were identified genome widely and selected genes validated by RT-PCR. We found that hypoxia induced HIF-1alpha, CA IX and VEGF expression but not HIF-2alpha in NPC cells. Microarray expression analysis showed that 222 genes were commonly up-regulated and 137 genes down-regulated in hypoxic-treated CNE-2 and HONE-1 cells. Hypoxia induced broad changes of both up- and down-regulated gene expressions involved in diverse biological processes in NPC cells. Elucidation of the coordinated functions modulated by hypoxia could lead to a better understanding of the clinical significance of the hypoxic tumor phenotype.
Authors:
Fion L Sung; Edwin P Hui; Qian Tao; Hongyu Li; Nancy B Y Tsui; Y M Dennis Lo; Brigette B Y Ma; Ka F To; Adrian L Harris; Anthony T C Chan
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-02-22
Journal Detail:
Title:  Cancer letters     Volume:  253     ISSN:  0304-3835     ISO Abbreviation:  Cancer Lett.     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-06-11     Completed Date:  2007-08-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  74-88     Citation Subset:  IM    
Affiliation:
Department of Clinical Oncology, State Key Laboratory in Oncology in South China, Sir YK Pao Centre for Cancer, Hong Kong Cancer Institute, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
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MeSH Terms
Descriptor/Qualifier:
Antigens, Neoplasm / metabolism
Basic Helix-Loop-Helix Transcription Factors / metabolism
Carbonic Anhydrases / metabolism
Cell Hypoxia
Cell Line, Tumor
Gene Expression*
Humans
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
Nasopharyngeal Neoplasms / genetics*
Oligonucleotide Array Sequence Analysis
Signal Transduction
Vascular Endothelial Growth Factor A / metabolism
Chemical
Reg. No./Substance:
0/Antigens, Neoplasm; 0/Basic Helix-Loop-Helix Transcription Factors; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/Vascular Endothelial Growth Factor A; 0/endothelial PAS domain-containing protein 1; EC 4.2.1.1/CA9 protein, human; EC 4.2.1.1/Carbonic Anhydrases

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