title: Activity of heme oxygenase-1 affects expression levels of hypoxia inducible factor-1 gene in vitro.
abstract: BACKGROUND
  One effect of solid tumors is severe hypoxia of local tissues. Heme oxygenase-1 (HO-1) is highly expressed in a variety of human tumor tissues; its induction and activity are closely related to growth of solid tumors. Hypoxia inducible factor-1 (HIF-1) is a transcription factor that regulates hypoxia signal transduction and plays a central role in tumor hypoxia regulation. However, whether and how changes in HO-1 activity affect HIF-1 gene expression has not been reported previously.
  
  
  METHODS
  Hypoxia-inducible models were established using gastric cancer cell lines (SGC-7901) in a hypoxia incubator. Cells were placed in four groups: Group A, transfected by plasmid harboring HO-1 shRNA; Group B, transfected with scrambled shRNA vector; Group C, treated with hemin; and Group D, exposed to hypoxia only. Expressions of HO-1 and HIF-1 mRNAs were quantified by reverse transcription-polymerase chain reaction. Expressions of HO-1 and HIF-1 proteins were determined by immunohistochemistry and Western blotting.
  
  
  RESULTS
  mRNA and protein levels of HO-1 and HIF-1 in the control group were significantly higher than in Group A (P < 0.01), but lower than in Group C (P < 0.01). Chromatin immunoprecipitation analysis showed that HIF-1 was identified as the direct HO-1 target gene.
  
  
  CONCLUSIONS
  While affected by HIF-1, HO-1 up-regulation promotes the expression of HIF-1 and the down-regulation of HO-1 suppresses the expression of HIF-1 gene.
authors.affiliation: Department of Surgery, Shandong Provincial Hospital, Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Rui-zheng
authors.initials: RZ
authors.lastname: Miao
authors.forename: Li-qing
authors.initials: LQ
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Zhang
authors.initials: Z
authors.lastname: Li
authors.forename: Le-ping
authors.initials: LP
authors.lastname: Li
authors.forename: Ren-le
authors.initials: RL
authors.lastname: Guo
authors.forename: Jian-feng
authors.initials: JF
authors.lastname: Li
authors.forename: Xiao-bo
authors.initials: XB
authors.lastname: Guo
mesh_terms: D015153:Blotting, Western; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051793:Hypoxia-Inducible Factor 1; D034741:RNA, Small Interfering; D051547:Heme Oxygenase-1