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dc.contributor.authorLogotheti, Stella
dc.contributor.authorPapaevangeliou, Dimitra
dc.contributor.authorMichalopoulos, Ioannis
dc.contributor.authorSideridou, Maria
dc.contributor.authorTsimaratou, Katerina
dc.contributor.authorChristodoulou, Ioannis
dc.contributor.authorPyrillou, Katerina
dc.contributor.authorGorgoulis, Vassilis
dc.contributor.authorVlahopoulos, Spiros
dc.contributor.authorZoumpourlis, Vassilis
dc.date.accessioned2018-10-03T04:46:05Z
dc.date.available2018-10-03T04:46:05Z
dc.date.issued2012
dc.identifier.issn1932-6203
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/283116
dc.description.abstractEstrogen receptors (ER), namely ERα and ERβ, are hormone-activated transcription factors with an important role in carcinogenesis. In the present study, we aimed at elucidating the implication of ERα in skin cancer, using chemically-induced mouse skin tumours, as well as cell lines representing distinct stages of mouse skin oncogenesis. First, using immunohistochemical staining we showed that ERα is markedly increased in aggressive mouse skin tumours in vivo as compared to the papilloma tumours, whereas ERβ levels are low and become even lower in the aggressive spindle tumours of carcinogen-treated mice. Then, using the multistage mouse skin carcinogenesis model, we showed that ERα gradually increases during promotion and progression stages of mouse skin carcinogenesis, peaking at the most aggressive stage, whereas ERβ levels only slightly change throughout skin carcinogenesis. Stable transfection of the aggressive, spindle CarB cells with a dominant negative form of ERα (dnERα) resulted in reduced ERα levels and reduced binding to estrogen responsive elements (ERE)-containing sequences. We characterized two highly conserved EREs on the mouse ERα promoter through which dnERα decreased endogenous ERα levels. The dnERα-transfected CarB cells presented altered protein levels of cytoskeletal and cell adhesion molecules, slower growth rate and impaired anchorage-independent growth in vitro, whereas they gave smaller tumours with extended latency period of tumour onset in vivo. Our findings suggest an implication of ERα in the aggressiveness of spindle mouse skin cancer cells, possibly through regulation of genes affecting cell shape and adhesion, and they also provide hints for the effective targeting of spindle cancer cells by dnERα.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherPublic Library of Science (PLoS)
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectCell Line
dc.subjectCytoskeleton
dc.subjectAnimals
dc.subjectMice
dc.subjectSkin Neoplasms
dc.subjectCell Transformation, Neoplastic
dc.subject9,10-Dimethyl-1,2-benzanthracene
dc.subjectNeoplasm Proteins
dc.subjectEstrogen Receptor alpha
dc.subjectEstrogen Receptor beta
dc.subjectCarcinogens
dc.subjectTransfection
dc.subjectCell Adhesion
dc.subjectGenes, Dominant
dc.titleProgression of mouse skin carcinogenesis is associated with increased ERα levels and is repressed by a dominant negative form of ERα.
dc.typeArticle
prism.issueIdentifier8
prism.publicationDate2012
prism.publicationNamePLoS One
prism.startingPagee41957
prism.volume7
dc.identifier.doi10.17863/CAM.30477
dcterms.dateAccepted2012-06-27
rioxxterms.versionofrecord10.1371/journal.pone.0041957
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2012-01
dc.contributor.orcidPyrillou, Katerina [0000-0003-0375-7810]
dc.identifier.eissn1932-6203
rioxxterms.typeJournal Article/Review
cam.issuedOnline2012-08-03


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International