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dc.contributor.authorKauffman, EC
dc.contributor.authorRobinson, BD
dc.contributor.authorDownes, M
dc.contributor.authorMarcinkiewicz, K
dc.contributor.authorVourganti, S
dc.contributor.authorScherr, DS
dc.contributor.authorGudas, LJ
dc.contributor.authorMongan, NP
dc.date.accessioned2017-05-03T13:52:38Z
dc.date.available2017-05-03T13:52:38Z
dc.date.issued2013
dc.date.modified2014-07-28T06:50:39Z
dc.identifier.issn1021-335X
dc.identifier.doi10.3892/or.2013.2416
dc.identifier.urihttp://hdl.handle.net/10072/61536
dc.description.abstractA role for estrogen signaling in urothelial carcinoma of the bladder (UCB) is suggested to be associated with more advanced disease with worse outcomes in women. Estrogen receptor ߠ(ERߩ is the predominant receptor in bladder tissues. We aimed to ascertain whether ERߠcorrelates with clinicopathological predictors of aggressive bladder cancer and worse survival outcomes. ERߠwas measured by immunohistochemistry in malignant and adjacent benign bladder tissues in patients (N=72) with UCB who underwent radical cystectomy. ERߠexpression was tested for statistical association with clinicopathological variables and patient survival. ERߠexpression was determined in bladder cancer cell lines, and the effects of the selective estrogen modulator tamoxifen and the ERߠagonist diarylpropionitrile on cell growth were determined. The ERߠlevel was significantly higher in malignant vs. benign urothelium (P<0.001) and was strongly associated with aggressive tumor histology characterized by lymphovascular (P=0.008) and perineural (P=0.006) invasion, and clinical histories of pelvic irradiation (P=0.005), hydronephrosis (P=0.022) and no intravesical chemotherapy (P=0.038). All patients with a high (>70%) percentage of ERߠpositivity in tissue with >3-month follow-up developed recurrent disease (P=0.009). Higher ERߠlevel was predictive of worse recurrence-free and overall survival following cystectomy, after adjustment for tumor stage, and remained significantly associated with recurrence-free survival in the multivariable analysis including tumor stage, nodal stage and lymphovascular invasion. Activation of ERߠin bladder cancer cell lines led to significant increases in proliferation, while pharmacological inhibition with tamoxifen blocked cell growth. Our study supports a role for ERߠin aggressive UCB. Pharmacological targeting of ERߠwarrants further investigation as a therapeutic strategy in UCB.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.format.extent840470 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglish
dc.language.isoeng
dc.publisherSpandidos Publications
dc.publisher.placeGreece
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom131
dc.relation.ispartofpageto138
dc.relation.ispartofissue1
dc.relation.ispartofjournalOncology Reports
dc.relation.ispartofvolume30
dc.rights.retentionY
dc.subject.fieldofresearchOncology and carcinogenesis
dc.subject.fieldofresearchOncology and carcinogenesis not elsewhere classified
dc.subject.fieldofresearchcode3211
dc.subject.fieldofresearchcode321199
dc.titleEstrogen receptor-β expression and pharmacological targeting in bladder cancer
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.rights.copyright© 2013 Spandidos Publications. The attached file is reproduced here in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.
gro.date.issued2013
gro.hasfulltextFull Text
gro.griffith.authorDownes, Martin J.


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