title: Loss of MAL expression in precancerous lesions of the esophagus.
abstract: BACKGROUND
  We have identified a novel function of MAL (T-cell differentiation-related gene) as a candidate suppressor gene in esophageal cancer. As the role of MAL expression in esophageal carcinogenesis is as yet undetermined, MAL expression in a rat multi-step carcinogenic model and in precancerous lesions of the human esophagus was investigated. Microarray analysis between MAL-transfectant and control cells was also carried out to clarify how MAL confers its anti-tumor effects.
  
  
  METHODS
  (1) In the rat model, MAL expression levels in laser microdissected normal esophageal epithelium, dysplastic tissues and carcinoma tissues were examined by reverse transcription (RT)-PCR. (2) Immunostaining with MAL antibody was performed in 10 dysplastic lesions adjacent to cancer in six cases of esophageal cancer. (3) We established a MAL transfectant using a Tet-off vector in esophageal cancer cells and performed microarray analysis under MAL-positive and MAL-negative conditions.
  
  
  RESULTS
  (1) In the rat model, MAL mRNA expression was observed only in the normal samples. (2) MAL expression was observed distinctively in differentiated or keratinized normal tissues and was not observed in either dysplastic lesions or carcinoma tissue. (3) Up-regulated genes in MAL-positive cells included keratin 18 (transfectant/control = 2.94) and keratin 10 (t/c = 2.82).
  
  
  CONCLUSIONS
  MAL expression was lost in dysplastic lesions of the rat carcinoma model as well as the human esophagus. The up-regulated keratins revealed by microarray analysis and the strong staining of the differentiated normal tissues in immunohistochemical study support the role of MAL as a regulator of differentiation in esophageal epithelium.
authors.affiliation: Department of Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu, 874-0838, Japan. mmori@beppu.kyushu-u.ac.jp
authors.forename: Koshi
authors.initials: K
authors.lastname: Mimori
authors.forename: Kohjiro
authors.initials: K
authors.lastname: Nishida
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ieta
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Yoshikawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sasaki
authors.forename: Hideshi
authors.initials: H
authors.lastname: Ishii
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Alonso
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004947:Esophagus / Q000378:metabolism / Q000473:pathology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D020411:Oligonucleotide Array Sequence Analysis; D010212:Papilloma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D011510:Proteolipids / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: C569026:MAL protein, human; C569028:Mal protein, rat; D026901:Membrane Transport Proteins; D009185:Myelin Proteins; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D011510:Proteolipids; D012334:RNA, Neoplasm