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Article: Aberrant activation of hedgehog signaling pathway contributes to endometrial carcinogenesis through Β-catenin
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TitleAberrant activation of hedgehog signaling pathway contributes to endometrial carcinogenesis through Β-catenin
 
AuthorsLiao, X1
Siu, MKY1
Au, CWH1
Chan, QKY1
Chan, HY1
Wong, ESY1
Ip, PPC1
Ngan, HYS1
Cheung, ANY1
 
KeywordsB-catenin
Endometrial cancers
Gli1
 
Issue Date2009
 
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/modpathol/
 
CitationModern Pathology, 2009, v. 22 n. 6, p. 839-847 [How to Cite?]
DOI: http://dx.doi.org/10.1038/modpathol.2009.45
 
AbstractThe hedgehog and Wnt signaling pathways play important roles in human cancers with possible interaction. This study aimed at analysis and correlation of the expression of Gli1, a transcriptional factor and target gene of hedgehog signaling pathway, with clinicopathological parameters and expression of Β-catenin, an important member of the Wnt pathway, in normal, hyperplastic and malignant endometrium. Immunohistochemical study on 15 normal endometrium, 14 simple and complex hyperplasia without atypia, 37 atypical complex hyperplasia and 80 endometrial cancers showed significant Gli1 overexpression and Β-catenin nuclear immunoreactivity in endometrial cancers and atypical endometrial hyperplasia when compared with normal endometrium (P0.05). Overexpression of Gli1 in endometrial cancers correlated with well-differentiated histological grade (P0.001), non-myometrial invasion (P0.004) and superficial myometrial invasion (P0.041). Β-Catenin nuclear immunoreactivity was also associated with well-differentiated histology (P0.013). Gli1 overexpression positively correlated with Β-catenin nuclear immunoreactivity in atypical complex hyperplasia (P0.013) and endometrial carcinoma (P0.017). Similar Gli1 and Β-catenin protein expression pattern was observed in normal and endometrial cancer cell lines by western blotting. We further showed a complex formation between Gli1 and Β-catenin protein in endometrial cancer cell lines in an immunoprecipitation study. Ectopic overexpression of Gli1 into endometrial cancer cells led to reduced expression of Β-catenin in cell cytoplasm and increased expression of Β-catenin in the nuclei. In summary, overexpression of Gli1 was an early event in endometrial carcinogenesis. Aberrant activation of hedgehog pathway may play important roles in endometrial cancer through Β-catenin nuclear accumulation. © 2009 USCAP, Inc. All rights reserved.
 
ISSN0893-3952
2013 Impact Factor: 6.364
 
DOIhttp://dx.doi.org/10.1038/modpathol.2009.45
 
ISI Accession Number IDWOS:000266504000013
Funding AgencyGrant Number
University of Hong Kong Conference and Research
Funding Information:

We thank Dr Hiroshi Sasaki at Riken Center for Developmental Biology, Kobe, Japan for providing us pcDNA3.1-HisB-hGli1 and Professor Doris Benbrook, University of Oklahoma Health Sciences Center, for the NEM cell line. The study was supported by the University of Hong Kong Conference and Research Grant.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorLiao, X
 
dc.contributor.authorSiu, MKY
 
dc.contributor.authorAu, CWH
 
dc.contributor.authorChan, QKY
 
dc.contributor.authorChan, HY
 
dc.contributor.authorWong, ESY
 
dc.contributor.authorIp, PPC
 
dc.contributor.authorNgan, HYS
 
dc.contributor.authorCheung, ANY
 
dc.date.accessioned2010-05-31T04:09:10Z
 
dc.date.available2010-05-31T04:09:10Z
 
dc.date.issued2009
 
dc.description.abstractThe hedgehog and Wnt signaling pathways play important roles in human cancers with possible interaction. This study aimed at analysis and correlation of the expression of Gli1, a transcriptional factor and target gene of hedgehog signaling pathway, with clinicopathological parameters and expression of Β-catenin, an important member of the Wnt pathway, in normal, hyperplastic and malignant endometrium. Immunohistochemical study on 15 normal endometrium, 14 simple and complex hyperplasia without atypia, 37 atypical complex hyperplasia and 80 endometrial cancers showed significant Gli1 overexpression and Β-catenin nuclear immunoreactivity in endometrial cancers and atypical endometrial hyperplasia when compared with normal endometrium (P0.05). Overexpression of Gli1 in endometrial cancers correlated with well-differentiated histological grade (P0.001), non-myometrial invasion (P0.004) and superficial myometrial invasion (P0.041). Β-Catenin nuclear immunoreactivity was also associated with well-differentiated histology (P0.013). Gli1 overexpression positively correlated with Β-catenin nuclear immunoreactivity in atypical complex hyperplasia (P0.013) and endometrial carcinoma (P0.017). Similar Gli1 and Β-catenin protein expression pattern was observed in normal and endometrial cancer cell lines by western blotting. We further showed a complex formation between Gli1 and Β-catenin protein in endometrial cancer cell lines in an immunoprecipitation study. Ectopic overexpression of Gli1 into endometrial cancer cells led to reduced expression of Β-catenin in cell cytoplasm and increased expression of Β-catenin in the nuclei. In summary, overexpression of Gli1 was an early event in endometrial carcinogenesis. Aberrant activation of hedgehog pathway may play important roles in endometrial cancer through Β-catenin nuclear accumulation. © 2009 USCAP, Inc. All rights reserved.
 
dc.description.naturelink_to_OA_fulltext
 
dc.identifier.citationModern Pathology, 2009, v. 22 n. 6, p. 839-847 [How to Cite?]
DOI: http://dx.doi.org/10.1038/modpathol.2009.45
 
dc.identifier.citeulike4240859
 
dc.identifier.doihttp://dx.doi.org/10.1038/modpathol.2009.45
 
dc.identifier.epage847
 
dc.identifier.hkuros161649
 
dc.identifier.hkuros166977
 
dc.identifier.isiWOS:000266504000013
Funding AgencyGrant Number
University of Hong Kong Conference and Research
Funding Information:

We thank Dr Hiroshi Sasaki at Riken Center for Developmental Biology, Kobe, Japan for providing us pcDNA3.1-HisB-hGli1 and Professor Doris Benbrook, University of Oklahoma Health Sciences Center, for the NEM cell line. The study was supported by the University of Hong Kong Conference and Research Grant.

 
dc.identifier.issn0893-3952
2013 Impact Factor: 6.364
 
dc.identifier.issue6
 
dc.identifier.openurl
 
dc.identifier.pmid19329935
 
dc.identifier.scopuseid_2-s2.0-67349260818
 
dc.identifier.spage839
 
dc.identifier.urihttp://hdl.handle.net/10722/60364
 
dc.identifier.volume22
 
dc.languageeng
 
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/modpathol/
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofModern Pathology
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshEndometrial Neoplasms - genetics - metabolism - pathology
 
dc.subject.meshHedgehog Proteins - metabolism
 
dc.subject.meshSignal Transduction - physiology
 
dc.subject.meshTranscription Factors - metabolism
 
dc.subject.meshbeta Catenin - metabolism
 
dc.subjectB-catenin
 
dc.subjectEndometrial cancers
 
dc.subjectGli1
 
dc.titleAberrant activation of hedgehog signaling pathway contributes to endometrial carcinogenesis through Β-catenin
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong