title: Activation of sonic hedgehog signaling pathway in olfactory neuroblastoma.
abstract: OBJECTIVE
  Sonic hedgehog (Shh) signaling pathway is associated with tumor development; however, the role of Shh signaling in the development of olfactory neuroblastoma (ONB) is unknown. This study aimed to investigate the relationship between the regulation of Shh signaling and the pathogenesis of ONB.
  
  
  METHODS
  The expression of Shh signaling components was characterized by immunohistochemistry in human non-tumor olfactory epithelium and ONB specimens, and by RT-PCR and immunoblotting in human ONB cell lines. The impact of the treatment with cyclopamine (a selective inhibitor of the Shh pathway) and/or exogenous Shh on ONB cell proliferation, cycle and apoptosis was examined by MTT, soft agar colony formation and flow cytometry assays, respectively. The influence of Shh signaling on the expression of Shh signaling components and cell cycle-related regulators was determined by immunoblotting and quantitative RT-PCR, respectively.
  
  
  RESULTS
  The expression of Pacthed1, Gli1 and Gli2 was detected in 70, 70, and 65% of human ONB specimens, respectively, and in proportion of ONB cell lines, but not in non-tumor olfactory epithelium. Treatment with cyclopamine inhibited the proliferation and colony formation of ONB cells, induced ONB cell cycle arrest and apoptosis, and down-regulated the expression of Pacthed1, Gli1 and cyclin D1, but up-regulated p21 expression in vitro. These regulatory effects of cyclopamine were partially or completely erased by exogenous Shh.
  
  
  CONCLUSIONS
  These data suggest that the Shh signaling pathway is crucial for the growth of ONB.
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Mao
authors.forename: Yuan-Peng
authors.initials: YP
authors.lastname: Xia
authors.forename: Yu-Nan
authors.initials: YN
authors.lastname: Zhou
authors.forename: Ruo-Lian
authors.initials: RL
authors.lastname: Dai
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.forename: Yan-Jun
authors.initials: YJ
authors.lastname: Wang
authors.forename: Shu-Jie
authors.initials: SJ
authors.lastname: Duan
authors.forename: Xian
authors.initials: X
authors.lastname: Qiao
authors.forename: Yuan-Wu
authors.initials: YW
authors.lastname: Mei
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
mesh_terms: D017209:Apoptosis; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018304:Esthesioneuroblastoma, Olfactory / Q000378:metabolism* / Q000473:pathology; D053823:Hedgehog Proteins / Q000502:physiology*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000032:analysis / Q000235:genetics; D009296:Nasal Cavity; D009669:Nose Neoplasms / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics; D000072079:Patched Receptors; D011956:Receptors, Cell Surface / Q000032:analysis / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2
chemical_list: C400551:GLI1 protein, human; C082593:GLI2 protein, human; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D000072079:Patched Receptors; D011956:Receptors, Cell Surface; C509239:SHH protein, human; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2