title: HIF-1α effects on angiogenic potential in human small cell lung carcinoma.
abstract: BACKGROUND
  Hypoxia-inducible factor-1 alpha (HIF-1α) maybe an important regulatory factor for angiogenesis of small cell lung cancer (SCLC). Our study aimed to investigate the effect of HIF-1α on angiogenic potential of SCLC including two points: One is the effect of HIF-1α on the angiogenesis of SCLC in vivo. The other is the regulation of angiogenic genes by HIF-1α in vitro and in vivo.
  
  
  METHODS
  In vivo we used an alternative method to study the effect of HIF-1a on angiogenic potential of SCLC by buliding NCI-H446 cell transplantation tumor on the chick embryo chorioallantoic membrane (CAM) surface. In vitro we used microarray to screen out the angiogenic genes regulated by HIF-1a and tested their expression level in CAM transplantation tumor by RT-PCR and Western-blot analysis.
  
  
  RESULTS
  In vivo angiogenic response surrounding the SCLC transplantation tumors in chick embryo chorioallantoic membrane (CAM) was promoted after exogenous HIF-1α transduction (p < 0.05). In vitro the changes of angiogenic genes expression induced by HIF-1α in NCI-H446 cells were analyzed by cDNA microarray experiments. HIF-1α upregulated the expression of angiogenic genes VEGF-A, TNFAIP6, PDGFC, FN1, MMP28, MMP14 to 6.76-, 6.69-, 2.26-, 2.31-, 4.39-, 2.97- fold respectively and glycolytic genes GLUT1, GLUT2 to2.98-, 3.74- fold respectively. In addition, the expression of these angiogenic factors were also upregulated by HIF-1α in the transplantion tumors in CAM as RT-PCR and Western-blot analysis indicated.
  
  
  CONCLUSIONS
  These results indicated that HIF-1α may enhance the angiogenic potential of SCLC by regulating some angiogenic genes such as VEGF-A, MMP28 etc. Therefore, HIF-1α may be a potential target for the gene targeted therapy of SCLC.
authors.affiliation: Department of Thoracic Surgery, First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wan
authors.forename: Huiping
authors.initials: H
authors.lastname: Chai
authors.forename: Zaicheng
authors.initials: Z
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Ge
authors.forename: Ningning
authors.initials: N
authors.lastname: Kang
authors.forename: Wanli
authors.initials: W
authors.lastname: Xia
authors.forename: Yun
authors.initials: Y
authors.lastname: Che
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D055752:Small Cell Lung Carcinoma / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger