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Article: Aberrant activation of hedgehog signaling pathway contributes to endometrial carcinogenesis through Β-catenin

TitleAberrant activation of hedgehog signaling pathway contributes to endometrial carcinogenesis through Β-catenin
Authors
KeywordsB-catenin
Endometrial cancers
Gli1
Issue Date2009
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/modpathol/
Citation
Modern Pathology, 2009, v. 22 n. 6, p. 839-847 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/60364
ISSN
2014 Impact Factor: 6.187
2014 SCImago Journal Rankings: 2.642
ISI Accession Number ID
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.

References

 

DC FieldValueLanguage
dc.contributor.authorLiao, Xen_HK
dc.contributor.authorSiu, MKYen_HK
dc.contributor.authorAu, CWHen_HK
dc.contributor.authorChan, QKYen_HK
dc.contributor.authorChan, HYen_HK
dc.contributor.authorWong, ESYen_HK
dc.contributor.authorIp, PPCen_HK
dc.contributor.authorNgan, HYSen_HK
dc.contributor.authorCheung, ANYen_HK
dc.date.accessioned2010-05-31T04:09:10Z-
dc.date.available2010-05-31T04:09:10Z-
dc.date.issued2009en_HK
dc.identifier.citationModern Pathology, 2009, v. 22 n. 6, p. 839-847en_HK
dc.identifier.issn0893-3952en_HK
dc.identifier.urihttp://hdl.handle.net/10722/60364-
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.en_HK
dc.languageengen_HK
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/modpathol/en_HK
dc.relation.ispartofModern Pathologyen_HK
dc.subjectB-cateninen_HK
dc.subjectEndometrial cancersen_HK
dc.subjectGli1en_HK
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.titleAberrant activation of hedgehog signaling pathway contributes to endometrial carcinogenesis through Β-cateninen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0893-3952&volume=22&issue=6&spage=839&epage=847&date=2009&atitle=Aberrant+activation+of+hedgehog+signaling+pathway+contributes+to+endometrial+carcinogenesis+through+beta-catenin-
dc.identifier.emailSiu, MKY: mkysiu@hkucc.hku.hken_HK
dc.identifier.emailNgan, HYS: hysngan@hkucc.hku.hken_HK
dc.identifier.emailCheung, ANY: anycheun@hkucc.hku.hken_HK
dc.identifier.authoritySiu, MKY=rp00275en_HK
dc.identifier.authorityNgan, HYS=rp00346en_HK
dc.identifier.authorityCheung, ANY=rp00542en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1038/modpathol.2009.45en_HK
dc.identifier.pmid19329935en_HK
dc.identifier.scopuseid_2-s2.0-67349260818en_HK
dc.identifier.hkuros161649en_HK
dc.identifier.hkuros166977en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-67349260818&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume22en_HK
dc.identifier.issue6en_HK
dc.identifier.spage839en_HK
dc.identifier.epage847en_HK
dc.identifier.isiWOS:000266504000013-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridLiao, X=7202134156en_HK
dc.identifier.scopusauthoridSiu, MKY=24924018400en_HK
dc.identifier.scopusauthoridAu, CWH=22133897100en_HK
dc.identifier.scopusauthoridChan, QKY=8390404100en_HK
dc.identifier.scopusauthoridChan, HY=26024081600en_HK
dc.identifier.scopusauthoridWong, ESY=23101622300en_HK
dc.identifier.scopusauthoridIp, PPC=7003622683en_HK
dc.identifier.scopusauthoridNgan, HYS=34571944100en_HK
dc.identifier.scopusauthoridCheung, ANY=54927484100en_HK
dc.identifier.citeulike4240859-

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