Document Detail

Identification and characterization of demethylase JMJD1A as a gene upregulated in the human cellular response to hypoxia.
MedLine Citation:
PMID:  19471969     Owner:  NLM     Status:  MEDLINE    
Hypoxia is commonly found in human solid cancers and serves as a selective environment for the survival of aggressive cancer cells and as protection from anti-cancer therapies. In addition to a shift to anaerobic metabolism, the cellular response to hypoxia includes cessation of cell division and/or cell death. These mechanisms have still not been defined. Identification of the members of hypoxia-induced growth arrest pathways remain incomplete. We have undertaken an expression microarray analysis of the cellular response to hypoxia in diverse cell lines. An identified cohort of genes is reliably upregulated in various cells in response to hypoxia, as validated by reverse-transcriptase polymerase chain reaction (RT-PCR). One of the upregulated targets corresponds to an expressed sequence tag encoded by JMJD1A (a gene also known as JHDM2A), which has been identified as a histone demethylase that regulates the transcription of androgen receptor targets. We confirm, by RT-PCR, the upregulation of JMJD1A after hypoxia and desferroxamine treatment in multiple cell lines. We also show that JMJD1A is predominantly, but not exclusively, a nuclear protein. Immunofluorescent staining of HeLa cells shows a shift of cytoplasmic JMJD1A into the nucleus on hypoxia treatment. Immunohistochemical staining has revealed that JMJD1A is widely expressed in tissues, even in cells that are not known to express the androgen receptor, and is significantly increased in smooth muscle cells upon hypoxia treatment.
Aylin Sar; Dragana Ponjevic; Monica Nguyen; Adrian Harold Box; Douglas James Demetrick
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-05-27
Journal Detail:
Title:  Cell and tissue research     Volume:  337     ISSN:  1432-0878     ISO Abbreviation:  Cell Tissue Res.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-07-28     Completed Date:  2009-10-08     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0417625     Medline TA:  Cell Tissue Res     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  223-34     Citation Subset:  IM    
The Department of Pathology, University of Calgary, AB, Canada.
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MeSH Terms
Cell Hypoxia / genetics,  physiology
Gene Expression Regulation*
Hela Cells
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
Jumonji Domain-Containing Histone Demethylases
Oligonucleotide Array Sequence Analysis
Oxidoreductases, N-Demethylating / genetics*,  metabolism*
Up-Regulation / physiology
Reg. No./Substance:
0/HIF1A protein, human; 0/Hypoxia-Inducible Factor 1, alpha Subunit; EC 1.14.11.-/Jumonji Domain-Containing Histone Demethylases; EC 1.14.11.-/KDM3A protein, human; EC 1.5.-/Oxidoreductases, N-Demethylating

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