The level of claudin-7 is reduced as an early event in colorectal carcinogenesis
<p>Abstract</p> <p>Background</p> <p>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 maintai...
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Format: | Article |
Language: | English |
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BMC
2011-02-01
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Series: | BMC Cancer |
Online Access: | http://www.biomedcentral.com/1471-2407/11/65 |
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author | Tveit Kjell M Ikdahl Tone Lothe Inger MB Bisgaard Hanne C Santoni-Rugiu Eric Poulsen Steen S Godiksen Sine Friis Stine Bornholdt Jette Johnson Egil Kure Elin H Vogel Lotte K |
author_facet | Tveit Kjell M Ikdahl Tone Lothe Inger MB Bisgaard Hanne C Santoni-Rugiu Eric Poulsen Steen S Godiksen Sine Friis Stine Bornholdt Jette Johnson Egil Kure Elin H Vogel Lotte K |
author_sort | Tveit Kjell M |
collection | DOAJ |
description | <p>Abstract</p> <p>Background</p> <p>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 <it>in vivo </it>and <it>in vitro</it>. We found in an <it>in-silico </it>search tight co-regulation between <it>matriptase </it>and <it>claudin-7 </it>expression. We have previously shown that the <it>matriptase </it>expression level decreases during colorectal carcinogenesis. In the present study we investigated whether <it>claudin-7 </it>expression is likewise decreased during colorectal carcinogenesis, thereby causing or contributing to the compromised epithelial leakiness of dysplastic tissue.</p> <p>Methods</p> <p>The mRNA level of <it>claudin-7 </it>(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.</p> <p>Results</p> <p>A 2.7-fold reduction in the <it>claudin-7 </it>mRNA level was found when comparing the biopsies from healthy individuals with the biopsies of carcinomas (p < 0.001). Reductions in the <it>claudin-7 </it>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.</p> <p>Conclusions</p> <p>Our results show that the <it>claudin-7 </it>mRNA level is decreased already as an early event in colorectal carcinogenesis, probably contributing to the compromised epithelial barrier in adenomas.</p> |
first_indexed | 2024-12-14T01:18:49Z |
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id | doaj.art-851168388be0472eb9f570eb82ffa4ca |
institution | Directory Open Access Journal |
issn | 1471-2407 |
language | English |
last_indexed | 2024-12-14T01:18:49Z |
publishDate | 2011-02-01 |
publisher | BMC |
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series | BMC Cancer |
spelling | doaj.art-851168388be0472eb9f570eb82ffa4ca2022-12-21T23:22:30ZengBMCBMC Cancer1471-24072011-02-011116510.1186/1471-2407-11-65The level of claudin-7 is reduced as an early event in colorectal carcinogenesisTveit Kjell MIkdahl ToneLothe Inger MBBisgaard Hanne CSantoni-Rugiu EricPoulsen Steen SGodiksen SineFriis StineBornholdt JetteJohnson EgilKure Elin HVogel Lotte K<p>Abstract</p> <p>Background</p> <p>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 <it>in vivo </it>and <it>in vitro</it>. We found in an <it>in-silico </it>search tight co-regulation between <it>matriptase </it>and <it>claudin-7 </it>expression. We have previously shown that the <it>matriptase </it>expression level decreases during colorectal carcinogenesis. In the present study we investigated whether <it>claudin-7 </it>expression is likewise decreased during colorectal carcinogenesis, thereby causing or contributing to the compromised epithelial leakiness of dysplastic tissue.</p> <p>Methods</p> <p>The mRNA level of <it>claudin-7 </it>(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.</p> <p>Results</p> <p>A 2.7-fold reduction in the <it>claudin-7 </it>mRNA level was found when comparing the biopsies from healthy individuals with the biopsies of carcinomas (p < 0.001). Reductions in the <it>claudin-7 </it>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.</p> <p>Conclusions</p> <p>Our results show that the <it>claudin-7 </it>mRNA level is decreased already as an early event in colorectal carcinogenesis, probably contributing to the compromised epithelial barrier in adenomas.</p>http://www.biomedcentral.com/1471-2407/11/65 |
spellingShingle | Tveit Kjell M Ikdahl Tone Lothe Inger MB Bisgaard Hanne C Santoni-Rugiu Eric Poulsen Steen S Godiksen Sine Friis Stine Bornholdt Jette Johnson Egil Kure Elin H Vogel Lotte K The level of claudin-7 is reduced as an early event in colorectal carcinogenesis BMC Cancer |
title | The level of claudin-7 is reduced as an early event in colorectal carcinogenesis |
title_full | The level of claudin-7 is reduced as an early event in colorectal carcinogenesis |
title_fullStr | The level of claudin-7 is reduced as an early event in colorectal carcinogenesis |
title_full_unstemmed | The level of claudin-7 is reduced as an early event in colorectal carcinogenesis |
title_short | The level of claudin-7 is reduced as an early event in colorectal carcinogenesis |
title_sort | level of claudin 7 is reduced as an early event in colorectal carcinogenesis |
url | http://www.biomedcentral.com/1471-2407/11/65 |
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