title: The level of claudin-7 is reduced as an early event in colorectal carcinogenesis.
abstract: BACKGROUND
  Compromised epithelial barriers are found in dysplastic tissue of the gastrointestinal tract. Claudins are transmembrane proteins important for tight junctions. Claudins regulate the paracellular transport and are crucial for maintaining a functional epithelial barrier. Down-regulation of the oncogenic serine protease, matriptase, induces leakiness in epithelial barriers both in vivo and in vitro. We found in an in-silico search tight co-regulation between matriptase and claudin-7 expression. We have previously shown that the matriptase expression level decreases during colorectal carcinogenesis. In the present study we investigated whether claudin-7 expression is likewise decreased during colorectal carcinogenesis, thereby causing or contributing to the compromised epithelial leakiness of dysplastic tissue.
  
  
  METHODS
  The mRNA level of claudin-7 (CLDN7) was determined in samples from 18 healthy individuals, 100 individuals with dysplasia and 121 colorectal cancer patients using quantitative real time RT-PCR. In addition, immunohistochemical stainings were performed on colorectal adenomas and carcinomas, to confirm the mRNA findings.
  
  
  RESULTS
  A 2.7-fold reduction in the claudin-7 mRNA level was found when comparing the biopsies from healthy individuals with the biopsies of carcinomas (p < 0.001). Reductions in the claudin-7 mRNA levels were also detected in mild/moderate dysplasia (p < 0.001), severe dysplasia (p < 0.01) and carcinomas (p < 0.01), compared to a control sample from the same individual. The decrease at mRNA level was confirmed at the protein level by immunohistochemical stainings.
  
  
  CONCLUSIONS
  Our results show that the claudin-7 mRNA level is decreased already as an early event in colorectal carcinogenesis, probably contributing to the compromised epithelial barrier in adenomas.
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Health Science, University of Copenhagen, Denmark.
authors.forename: Jette
authors.initials: J
authors.lastname: Bornholdt
authors.forename: Stine
authors.initials: S
authors.lastname: Friis
authors.forename: Sine
authors.initials: S
authors.lastname: Godiksen
authors.forename: Steen S
authors.initials: SS
authors.lastname: Poulsen
authors.forename: Eric
authors.initials: E
authors.lastname: Santoni-Rugiu
authors.forename: Hanne C
authors.initials: HC
authors.lastname: Bisgaard
authors.forename: Inger M B
authors.initials: IM
authors.lastname: Lothe
authors.forename: Tone
authors.initials: T
authors.lastname: Ikdahl
authors.forename: Kjell M
authors.initials: KM
authors.lastname: Tveit
authors.forename: Egil
authors.initials: E
authors.lastname: Johnson
authors.forename: Elin H
authors.initials: EH
authors.lastname: Kure
authors.forename: Lotte K
authors.initials: LK
authors.lastname: Vogel
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D057167:Claudins; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D055088:Early Detection of Cancer; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D008954:Models, Biological
chemical_list: C473255:CLDN7 protein, human; D057167:Claudins; D008565:Membrane Proteins