title: Expression of KL-6/MUC1 in pancreatic ductal carcinoma and its potential relationship with β-catenin in tumor progression.
abstract: OBJECTIVE
  The aim of this study was to evaluate the expression of Krebs yon den Lundgen-6/Mucin 1 (KL-6/MUC1) in pancreatic ductal carcinoma and its potential relationship with β-catenin in tumor progression.
  
  
  METHODS
  The expressions of KL-6/MUC1 and β-catenin in 18 cases of pancreatic ductal carcinoma were detected by immunohistochemical staining. To determine the impact of KL-6/MUC1 down-regulation on pancreatic ductal carcinoma progression, siRNA targeting MUC1 was used to knockdown KL-6/MUC1 expression. The down-regulation of KL-6/MUC1 expression was confirmed by reverse transcription-polymerase chain reaction and immunofluorescence staining. E-cadherin and E-cadherin/β-catenin complex expressions were determined by immunoprecipitation. The expressions of KL-6/MUC1, β-catenin, cyclin D1 and c-myc were detected by Western blot. Cell proliferation, apoptosis and invasive abilities were detected by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide assay, Annexin V-FITC apoptosis detection kit and invasion assay.
  
  
  RESULTS
  Positive KL-6/MUC1 staining was observed in the cancer tissues of all the 18 pancreatic ductal carcinoma cases (100.0%), and high nuclear β-catenin expression was seen in 12 cancers (66.7%). Reverse transcription-polymerase chain reaction and immunofluorescence staining showed that both KL-6/MUC1 mRNA and protein were effectively silenced by MUC1 siRNA. After KL-6/MUC1 knockdown, E-cadherin and E-cadherin/β-catenin complex expressions were increased, while the nuclear β-catenin, cyclin D1, and c-myc expressions were decreased. Down-regulation of KL-6/MUC1 also resulted in slower proliferation, increased apoptosis and decreased invasive ability.
  
  
  CONCLUSIONS
  This study indicated that KL-6/MUC1 played a complex role in regulating pancreatic ductal carcinoma cell proliferation, apoptosis, and invasion, and also supported the hypothesis that there is a functional link between KL-6/MUC1 expression and β-catenin subcellular localization.
authors.affiliation: Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, the University of Tokyo, Japan.
authors.forename: Huanli
authors.initials: H
authors.lastname: Xu
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Inagaki
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Seyama
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Sugawara
authors.forename: Guanhua
authors.initials: G
authors.lastname: Du
authors.forename: Fengshan
authors.initials: F
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kokudo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000235:genetics*; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C060192:MUC1 protein, human; D018396:Mucin-1; D051176:beta Catenin