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...

Full description

Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: BMC 2011-02-01
Series:BMC Cancer
Online Access:http://www.biomedcentral.com/1471-2407/11/65
_version_ 1818563623046348800
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
format Article
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
record_format Article
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
work_keys_str_mv AT tveitkjellm thelevelofclaudin7isreducedasanearlyeventincolorectalcarcinogenesis
AT ikdahltone thelevelofclaudin7isreducedasanearlyeventincolorectalcarcinogenesis
AT lotheingermb thelevelofclaudin7isreducedasanearlyeventincolorectalcarcinogenesis
AT bisgaardhannec thelevelofclaudin7isreducedasanearlyeventincolorectalcarcinogenesis
AT santonirugiueric thelevelofclaudin7isreducedasanearlyeventincolorectalcarcinogenesis
AT poulsensteens thelevelofclaudin7isreducedasanearlyeventincolorectalcarcinogenesis
AT godiksensine thelevelofclaudin7isreducedasanearlyeventincolorectalcarcinogenesis
AT friisstine thelevelofclaudin7isreducedasanearlyeventincolorectalcarcinogenesis
AT bornholdtjette thelevelofclaudin7isreducedasanearlyeventincolorectalcarcinogenesis
AT johnsonegil thelevelofclaudin7isreducedasanearlyeventincolorectalcarcinogenesis
AT kureelinh thelevelofclaudin7isreducedasanearlyeventincolorectalcarcinogenesis
AT vogellottek thelevelofclaudin7isreducedasanearlyeventincolorectalcarcinogenesis
AT tveitkjellm levelofclaudin7isreducedasanearlyeventincolorectalcarcinogenesis
AT ikdahltone levelofclaudin7isreducedasanearlyeventincolorectalcarcinogenesis
AT lotheingermb levelofclaudin7isreducedasanearlyeventincolorectalcarcinogenesis
AT bisgaardhannec levelofclaudin7isreducedasanearlyeventincolorectalcarcinogenesis
AT santonirugiueric levelofclaudin7isreducedasanearlyeventincolorectalcarcinogenesis
AT poulsensteens levelofclaudin7isreducedasanearlyeventincolorectalcarcinogenesis
AT godiksensine levelofclaudin7isreducedasanearlyeventincolorectalcarcinogenesis
AT friisstine levelofclaudin7isreducedasanearlyeventincolorectalcarcinogenesis
AT bornholdtjette levelofclaudin7isreducedasanearlyeventincolorectalcarcinogenesis
AT johnsonegil levelofclaudin7isreducedasanearlyeventincolorectalcarcinogenesis
AT kureelinh levelofclaudin7isreducedasanearlyeventincolorectalcarcinogenesis
AT vogellottek levelofclaudin7isreducedasanearlyeventincolorectalcarcinogenesis