title: Hypoxia-inducible factor-1alpha is associated with angiogenesis, and expression of bFGF, PDGF-BB, and EGFR in invasive breast cancer.
abstract: OBJECTIVE
  Hypoxia-inducible factor-1 (HIF-1) is the key transcription factor regulating the cellular response to hypoxia, including angiogenesis. Growth factors play an important role in tumour growth and angiogenesis and some have been shown to be induced by HIF-1 in vitro. This study investigated if angiogenesis or growth factors or their receptors are associated with HIF-1alpha in invasive breast cancer.
  
  
  RESULTS
  High levels of HIF-1alpha, detected by immunohistochemistry in 45 breast cancers, were positively associated with increased microvessel density (as a measure of angiogenesis) (P = 0.023). Furthermore, high levels of HIF-1alpha were associated with epithelial expression (> or = 10%) of epidermal growth factor receptor (EGFR) (P = 0.011), platelet-derived growth factor (PDGF)-BB (P < 0.001), and basic fibroblast growth factor (bFGF) (P = 0.045). A positive, yet insignificant, trend for HIF-1alpha to be associated with epithelial expression of transforming growth factor (TGF)-alpha (P = 0.081) and vascular endothelial growth factor (VEGF) (P = 0.109) was noticed as well as an inverse association with stromal expression of TGF-beta-R1 (P = 0.070).
  
  
  CONCLUSIONS
  In invasive breast cancer, HIF-1alpha is associated with angiogenesis, and expression of growth factors bFGF and PDGF-BB, and the receptor EGFR. Thus, agents targeting HIF-1 may combine different pathways of inhibiting breast cancer growth, including angiogenesis and growth factors.
authors.affiliation: Department of Pathology, VU University Medical Centre, Amsterdam, Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Bos
authors.forename: P J
authors.initials: PJ
authors.lastname: van Diest
authors.forename: J S
authors.initials: JS
authors.lastname: de Jong
authors.forename: P
authors.initials: P
authors.lastname: van der Groep
authors.forename: P
authors.initials: P
authors.lastname: van der Valk
authors.forename: E
authors.initials: E
authors.lastname: van der Wall
mesh_terms: D019898:Autocrine Communication; D000077214:Becaplermin; D001943:Breast Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D018275:Carcinoma, Lobular / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D039621:Eukaryotic Initiation Factor-3; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D017154:Stromal Cells / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D039621:Eukaryotic Initiation Factor-3; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010982:Platelet-Derived Growth Factor; D011506:Proteins; D020574:Proto-Oncogene Proteins c-sis; D014157:Transcription Factors; D016211:Transforming Growth Factor alpha; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; C096013:EIF3I protein, human; D000077214:Becaplermin; D066246:ErbB Receptors