title: Regulation of the angiogenesis of acquired middle ear cholesteatomas by inhibitor of DNA binding transcription factor.
abstract: OBJECTIVE
  The aggressive growth of cholesteatoma in the middle ear involves the angiogenesis of the cholesteatomal perimatrix. However, which transcription factor is involved in this process remains unclear.
  
  
  OBJECTIVE
  To identify a transcription factor that supports the aggressive growth of cholesteatoma by controlling the angiogenesis of cholesteatoma in the middle ear milieu.
  
  
  METHODS
  We used clinical specimens for the profiling of angiogenic factors and their regulatory transcription factors in cholesteatoma. Human skin keratinocytes and endothelial cells were used for evaluation of the effects of candidate transcription factor on the angiogenic factor regulation and endothelial cell proliferation.
  
  
  METHODS
  University departments of otolaryngology-head and neck surgery.
  
  
  METHODS
  Eight clinical cholesteatomal and 8 control specimens were used for cellular and molecular biologic evaluation. An additional 8 cholesteatomal and 8 aural skin specimens were used for microarray studies.
  
  
  METHODS
  The expression of vascular endothelial growth factor, interleukin 8, and cyclooxygenase 2 as measured by means of immunohistochemistry and molecular biologic methods.
  
  
  RESULTS
  Human aural cholesteatomal specimens were rich in the expression of angiogenic factors such as vascular endothelial growth factor in the cholesteatomal matrix and perimatrix, accompanied by the transcription factor inhibitor of DNA binding (Id1). We found Id1 to be an essential regulator of vascular endothelial growth factor. In addition, potent angiogenic factors, including interleukin 8 and cyclooxygenase 2, were regulated by Id1 via different molecular mechanisms.
  
  
  CONCLUSIONS
  The transcription factor Id1 controls the angiogenesis of cholesteatoma through the regulation of vascular endothelial growth factor, interleukin 8, and cyclooxygenase 2, which are responsible for the angiogenesis of cholesteatoma. Id1 may serve as a good target for the treatment of cholesteatomal progression in the middle ear milieu.
authors: Department of Otolaryngology-Head and Neck Surgery, University of Minnesota, Minneapolis, MN 55455, USA.
authors: Shinji
authors: S
authors: Fukudome
authors: Chuan
authors: C
authors: Wang
authors: Yuki
authors: Y
authors: Hamajima
authors: Shengnan
authors: S
authors: Ye
authors: Yiqing
authors: Y
authors: Zheng
authors: Norihiko
authors: N
authors: Narita
authors: Hiroshi
authors: H
authors: Sunaga
authors: Shigeharu
authors: S
authors: Fujieda
authors: Xiaohua
authors: X
authors: Hu
authors: Ling
authors: L
authors: Feng
authors: Jizhen
authors: J
authors: Lin
mesh_terms: D002478:Cells, Cultured; D018424:Cholesteatoma, Middle Ear / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology; D008156:Luciferases; D046228:Microarray Analysis; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D016209:Interleukin-8; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D008156:Luciferases; D051546:Cyclooxygenase 2