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

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.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.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.DNA damage promotes carcinogenesis. This is clearly seen when DNA repair mechanisms are compromised. The eukaryotic cell takes many measures to prevent DNA damage, including formation of physical barriers to prevent the entry of carcinogens and other substances into the organism. In the gastrointestinal tract, a layer of polarised epithelial cells, held together by tight junctions and covered by a layer of mucus, forms a surprisingly efficient barrier. However, this barrier is often compromised already in dysplastic tissue [1]. This is likely to be a factor driving carcinogenesis by allowing carcinogens to enter the underlying tissue.In the intestine, molecules may pass the monolayer of epithelial cells, either by the transcellular route involving transcytosis or by the paracellular route crossing the tight junctions. Tight junctions are primarily located at the apical end of the lateral plasma membrane [2]. In addition to controlling the paracellular diffusion, tight junctions prevent the diffusion of membrane prot