The level of claudin-7 is reduced as an early event in colorectal carcinogenesis

BMC Cancer

Research Article

Sine Godiksen¹  Jette Bornholdt²  Hanne C Bisgaard²  Stine Friis²  Lotte K Vogel²  Egil Johnson³  Elin H Kure⁴  Steen S Poulsen⁵  Tone Ikdahl⁶  Kjell M Tveit⁶  Eric Santoni-Rugiu⁷  Inger MB Lothe⁸ 

[1] Department of Biology, Faculty of Science, University of Copenhagen, Copenhagen, Denmark;Department of Cellular and Molecular Medicine, Faculty of Health Science, University of Copenhagen, Denmark;Department of Gastroenterological Surgery, Oslo University Hospital, Oslo, Norway;Faculty of Medicine, University of Oslo, Oslo, Norway;Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway;Department of Environmental and Health Studies, Telemark University College, Bø, Norway;Department of Medical Anatomy, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark;Department of Oncology, Oslo University Hospital, Oslo, Norway;Department of Pathology, Diagnostic Center, Copenhagen University Hospital, Copenhagen, Denmark;Department of Pathology, Oslo University Hospital, Oslo, Norway;

关键词: Adenoma;    Tight Junction;    Normal Mucosa;    Epithelial Barrier;    Esophageal Squamous Cell Carcinoma Cell;   

DOI  :  10.1186/1471-2407-11-65

 received in 2010-09-27, accepted in 2011-02-10,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundCompromised 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.MethodsThe 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.ResultsA 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.ConclusionsOur 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.

【 授权许可】

Unknown   
© Bornholdt et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.