title: Cancer specific promoter CpG Islands hypermethylation of HOP homeobox (HOPX) gene and its potential tumor suppressive role in pancreatic carcinogenesis.
abstract: BACKGROUND
  We have recently identified HOP hoemobox (HOPX) as a tumor suppressor gene candidate, characterized by tumor-specific promoter DNA hypermethylation in human cancers, and it can remarkably inhibit tumors' aggressive phenotypes. In this current study, we for the first time examined methylation level of HOPX and tested the functional relevance in pancreatic cancer (PC).
  
  
  METHODS
  Clinical features of HOPX promoter hypermethylation was investigated in 89 PC tissues, and immunohistochemistry was added. We also examined its functional relevance in phenotype assays such as soft agar, proliferation, invasion, and cell cycle analysis.
  
  
  RESULTS
  PC tissues had HOPX gene hypermethylation as compared to the corresponding normal pancreas tissues, and its uniqueness was robust to discriminate tumor from normal tissues (AUC = 0.85, P < 0.0001). Unexpectedly, HOPX was increased in expression in tumor tissues, and immunohistochemistry revealed its predominant expression in the Langerhans islet cells, where HOPX was reduced in expression for PC cells with promoter hypermethylation. HOPX transfectants exhibited G1 arrest with subG1 accumulation, and inhibited tumor forming and invasive ability.
  
  
  CONCLUSIONS
  Defective expression of HOPX which is consistent with promoter DNA hypermethylation may explain aggressive phenotype of pancreatic cancer, and intense expression of HOPX in the Langerhans cells may in turn uniquely contribute to pancreatic carcinogenesis.
authors.affiliation: Department of Surgery, Kitasato University Hospital, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0375, Japan. komulu@hotmail.co.jp
authors.forename: Mina
authors.initials: M
authors.lastname: Waraya
authors.forename: Keishi
authors.initials: K
authors.lastname: Yamashita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Katoh
authors.forename: Akira
authors.initials: A
authors.lastname: Ooki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawamata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishimiya
authors.forename: Kazunori
authors.initials: K
authors.lastname: Nakamura
authors.forename: Akira
authors.initials: A
authors.lastname: Ema
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D001483:Base Sequence; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010179:Pancreas / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C476884:HOPX protein, human; D018398:Homeodomain Proteins; D025521:Tumor Suppressor Proteins