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dc.contributor.authorBornholdt, Jette
dc.contributor.authorFriis, Stine
dc.contributor.authorGodiksen, Sine
dc.contributor.authorPoulsen, Steen S.
dc.contributor.authorSantoni-Rugiu, Eric
dc.contributor.authorBisgaard, Hanne C.
dc.contributor.authorLothe, Inger Marie Bowitz
dc.contributor.authorAndersen, Tone Ikdahl
dc.contributor.authorTveit, Magne Kjell
dc.contributor.authorJohnson, Egil
dc.contributor.authorKure, Elin H.
dc.contributor.authorVogel, Lotte K.
dc.date.accessioned2012-04-04T07:22:37Z
dc.date.accessioned2017-04-19T12:25:05Z
dc.date.available2012-04-04T07:22:37Z
dc.date.available2017-04-19T12:25:05Z
dc.date.issued2011-02-10
dc.identifier.citationBornholdt, J., Friis, S., Godiksen, S., Poulsen, S.S., Santoni-Rugiu, E., Bisgaard, H.C., Lothe, I.M.B., Andersen, T.I., Tveit, M.K., Johnson, E., Kure, E.H. & Vogel, L.K. The level of claudin-7 is reduced as an early event in colorectal carcinogenesis. BMC Cancer, 2011, 11:65
dc.identifier.issn1471-2407
dc.identifier.urihttp://hdl.handle.net/11250/2438030
dc.description.abstractBACKGROUND: 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.
dc.language.isoeng
dc.publisherBioMed Central
dc.titleThe level of claudin-7 is reduced as an early event in colorectal carcinogenesis
dc.typeJournal article
dc.typePeer reviewed
dc.description.versionPublished version
dc.subject.nsi762
dc.source.journalBMC Cancer


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