Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/58940

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dc.contributor.authorReis-Filho, Jorge S.por
dc.contributor.authorSimpson, Pete T.por
dc.contributor.authorFulford, Laura G.por
dc.contributor.authorMartins, Albinopor
dc.contributor.authorSchmitt, Fernando C.por
dc.date.accessioned2019-02-06T12:29:01Z-
dc.date.issued2003-
dc.identifier.issn0344-0338-
dc.identifier.urihttp://hdl.handle.net/1822/58940-
dc.description.abstractDeltaN-p63 isoforms may act as oncogenes owing to their ability to bind to p53-reporter genes without inciting their transcription, thus blocking the p53-driven cell cycle arrest and apoptosis. A novel mechanism linking p63 and Wnt pathways has recently been proposed. Briefly, in vitro studies using squamous cell carcinoma cell lines have suggested that DeltaN-p63 may block the phosphorylation of beta-catenin, leading to its nuclear accumulation and triggering beta-catenin-responsive transcription of genes related to proliferation and oncogenic biological behavior. To test this new mechanism, the coexpression of DeltaN-p63 and beta-catenin was evaluated in a large cohort of human neoplasms.Two serial sections of TARP-4 multi-tumor tissue microarray, composed of 51 normal tissue cores and 400 human neoplasms [breast (n = 75), colon (n = 75), lung (n = 75), prostate (n = 75) and ovary (n = 50) neoplasms, melanoma (n = 25), and glioblastoma (n = 25)] were subjected to immunohistochemistry with DeltaN-p63 and beta-catenin monoclonal antibodies. p63 nuclear expression and beta-catenin membranous, cytoplasmic, membranous + cytoplasmic, and nuclear localization were evaluated.DeltaN-p63 expression and beta-catenin nuclear localization were found in 92.6% and 0% of squamous cell carcinomas, 8.9% and 0% of breast carcinomas, 13.8% and 0% of lung adenocarcinomas, 1.4% and 23.2% of colon adenocarcinomas, 0% and 4.8% of prostate adenocarcinomas, 11.1% and 5% of ovary carcinomas, 9.0% and 9.1% of malignant melanomas, and 12.5% and 40.0% of glioblastomas, respectively. No statistically significant association between DeltaN-p63 and nuclear beta-catenin expression was found for all tumors.At variance with squamous cell carcinoma cell lines, p63-driven nuclear accumulation of beta-catenin is an unusual phenomenon in human neoplasms. Caution should be exercised when translating the results of studies performed on cell lines to human neoplasms.por
dc.description.sponsorshipJS Reis-Filho is the recipient of the Gordon Signy International Fellowship Award and is partially supported by a PhD grant (Ref.: SFRH/BD/5386/2001) from the Fundação para a Ciência e a Tecnologia (FCT), Portugal and Programa Operacional Ciência, Tecnologia e Inovação (POCTI), Ref. POCTI/CBO/45157/2002.por
dc.language.isoengpor
dc.publisherUrban & Fischer Verlagpor
dc.relationSFRH/BD/5386/2001por
dc.relationinfo:eu-repo/grantAgreement/FCT/POCI/45157/PTpor
dc.rightsrestrictedAccesspor
dc.titlep63-driven nuclear accumulation of β-Catenin is not a frequent event in human neoplasmspor
dc.typearticlepor
dc.peerreviewedyespor
oaire.citationStartPage785por
oaire.citationEndPage793por
oaire.citationIssue12por
oaire.citationVolume199por
dc.identifier.doi10.1078/0344-0338-00497por
dc.identifier.pmid14989490por
dc.description.publicationversioninfo:eu-repo/semantics/publishedVersionpor
dc.subject.wosScience & Technologypor
sdum.journalPathology Research and Practicepor
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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