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    An in vivo hypoxia metagene identifies the novel hypoxia inducible factor target gene SLCO1B3.

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    Authors
    Ramachandran, A
    Betts, Guy N J
    Bhana, Sara
    Helme, Gemma
    Blick, C
    Moller-Levet, Carla S
    Saunders, Emma K
    Valentine, Helen R
    Pepper, Stuart D
    Miller, Crispin J
    Buffa, F
    Harris, A
    West, Catharine M L
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    Affiliation
    Cancer Research UK Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK.
    Issue Date
    2013-05
    
    Metadata
    Show full item record
    Abstract
    A hypoxia-associated gene signature (metagene) was previously derived via in vivo data-mining. In this study, we aimed to investigate whether this approach could identify novel hypoxia regulated genes. From an initial list of nine genes, three were selected for further study (BCAR1, IGF2BP2 and SLCO1B3). Ten cell lines were exposed to hypoxia and interrogated for the expression of the three genes. All three genes were hypoxia inducible in at least one of the 10 cell lines with SLCO1B3 induced in seven. SLCO1B3 was studied further using chromatin immunoprecipitation and luciferase assays to investigate hypoxia inducible factor (HIF) dependent transcription. Two functional HIF response elements were identified within intron 1 of the gene. The functional importance of SLCO1B3 was studied by gene knockdown experiments followed by cell growth assays, flow cytometry and Western blotting. SLCO1B3 knockdown reduced cell size and 3-dimensional spheroid volume, which was associated with decreased activation of the mammalian target of rapamycin (mTOR) pathway. Finally, Oncomine analysis revealed that head and neck and colorectal tumours had higher levels of SLCO1B3 compared to normal tissue. Thus, the knowledge based approach for deriving gene signatures can identify novel biologically relevant genes.
    Citation
    An in vivo hypoxia metagene identifies the novel hypoxia inducible factor target gene SLCO1B3. 2013, 49 (7):1741-51 Eur J Cancer
    Journal
    European Journal of Cancer
    URI
    http://hdl.handle.net/10541/295475
    DOI
    10.1016/j.ejca.2012.12.003
    PubMed ID
    23352438
    Type
    Article
    Language
    en
    ISSN
    1879-0852
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.ejca.2012.12.003
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