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Article: Aberrant activation of hedgehog signaling pathway in ovarian cancers: Effect on prognosis, cell invasion and differentiation

TitleAberrant activation of hedgehog signaling pathway in ovarian cancers: Effect on prognosis, cell invasion and differentiation
Authors
Issue Date2009
PublisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
Citation
Carcinogenesis, 2009, v. 30 n. 1, p. 131-140 How to Cite?
Abstract
Aberrant activation of hedgehog (HH) pathway has been implicated in the development of human malignancies. This study aimed at investigating the role of HH molecules in human ovarian carcinogenesis. The expression profiles of HH molecules were examined in ovarian tumor samples and ovarian cancer cell lines and the in vitro effects of HH molecules on cell proliferation, apoptosis, migration, invasion and cell differentiation as well as related downstream target genes were assessed. Overexpression of Patched and Gli1 protein in ovarian cancers correlated with poor survival of the patients (P = 0.008; P = 0.004). Significantly elevated expression of Sonic hedgehog messenger RNA was observed in ovarian cancers compared with normal tissues and benign ovarian tumors and such differential expression was specific to histological types (P < 0.05). Ectopic Gli1 overexpression in ovarian cancer cells conferred increased cell proliferation, cell mobility, invasiveness and change in differentiation in association with increased expression of E-cadherin, vimentin, Bcl-2, caspases as well as β1 integrin, membrane type 1 matrix metalloproteinase (MT1-MMP) and vascular endothelial growth factor (VEGF). Treatment with 3-keto-N-(aminoethyl-aminocaproyl-dihydrocinnamoyl)-cyclopamine induced cancer cell apoptosis, suppressed cell growth, mobility and invasiveness and induced cancer cell dedifferentiation with decreased expression of E-cadherin, cytokeratin 7, Snail, calretinin, vimentin, Bcl-2, caspases, β1 integrin, MT1-MMP and VEGF. Our data suggested that abnormal HH signaling activation plays important roles in the development and progression of ovarian cancers. Gli1 expression is an independent prognostic marker. Inhibition of the HH pathway molecules might be a valid therapeutic strategy for ovarian cancers. © The Author 2008. Published by Oxford University Press. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/60368
ISSN
2013 Impact Factor: 5.266
ISI Accession Number ID
References

 

Author Affiliations
  1. The University of Hong Kong
DC FieldValueLanguage
dc.contributor.authorLiao, Xen_HK
dc.contributor.authorSiu, MKYen_HK
dc.contributor.authorAu, CWHen_HK
dc.contributor.authorWong, ESYen_HK
dc.contributor.authorChan, HYen_HK
dc.contributor.authorIp, PPCen_HK
dc.contributor.authorNgan, HYSen_HK
dc.contributor.authorCheung, ANYen_HK
dc.date.accessioned2010-05-31T04:09:15Z-
dc.date.available2010-05-31T04:09:15Z-
dc.date.issued2009en_HK
dc.identifier.citationCarcinogenesis, 2009, v. 30 n. 1, p. 131-140en_HK
dc.identifier.issn0143-3334en_HK
dc.identifier.urihttp://hdl.handle.net/10722/60368-
dc.description.abstractAberrant activation of hedgehog (HH) pathway has been implicated in the development of human malignancies. This study aimed at investigating the role of HH molecules in human ovarian carcinogenesis. The expression profiles of HH molecules were examined in ovarian tumor samples and ovarian cancer cell lines and the in vitro effects of HH molecules on cell proliferation, apoptosis, migration, invasion and cell differentiation as well as related downstream target genes were assessed. Overexpression of Patched and Gli1 protein in ovarian cancers correlated with poor survival of the patients (P = 0.008; P = 0.004). Significantly elevated expression of Sonic hedgehog messenger RNA was observed in ovarian cancers compared with normal tissues and benign ovarian tumors and such differential expression was specific to histological types (P < 0.05). Ectopic Gli1 overexpression in ovarian cancer cells conferred increased cell proliferation, cell mobility, invasiveness and change in differentiation in association with increased expression of E-cadherin, vimentin, Bcl-2, caspases as well as β1 integrin, membrane type 1 matrix metalloproteinase (MT1-MMP) and vascular endothelial growth factor (VEGF). Treatment with 3-keto-N-(aminoethyl-aminocaproyl-dihydrocinnamoyl)-cyclopamine induced cancer cell apoptosis, suppressed cell growth, mobility and invasiveness and induced cancer cell dedifferentiation with decreased expression of E-cadherin, cytokeratin 7, Snail, calretinin, vimentin, Bcl-2, caspases, β1 integrin, MT1-MMP and VEGF. Our data suggested that abnormal HH signaling activation plays important roles in the development and progression of ovarian cancers. Gli1 expression is an independent prognostic marker. Inhibition of the HH pathway molecules might be a valid therapeutic strategy for ovarian cancers. © The Author 2008. Published by Oxford University Press. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/en_HK
dc.relation.ispartofCarcinogenesisen_HK
dc.rightsCarcinogenesis. Copyright © Lippincott Williams & Wilkins.en_HK
dc.subject.meshCell Differentiationen_HK
dc.subject.meshCell Line, Tumoren_HK
dc.subject.meshFemaleen_HK
dc.subject.meshHedgehog Proteins - metabolismen_HK
dc.subject.meshHumansen_HK
dc.subject.meshImmunohistochemistryen_HK
dc.subject.meshNeoplasm Invasivenessen_HK
dc.subject.meshOvarian Neoplasms - metabolism - pathologyen_HK
dc.subject.meshPrognosisen_HK
dc.subject.meshReceptors, Cell Surface - metabolismen_HK
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_HK
dc.subject.meshSignal Transductionen_HK
dc.subject.meshTranscription Factors - metabolismen_HK
dc.titleAberrant activation of hedgehog signaling pathway in ovarian cancers: Effect on prognosis, cell invasion and differentiationen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0147-4006&volume=30&spage=131&epage=140&date=2009&atitle=Aberrant+activation+of+hedgehog+signaling+pathway+in+ovarian+cancers:+effect+on+prognosis,+cell+invasion+and+differentiation.en_HK
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.doi10.1093/carcin/bgn230en_HK
dc.identifier.pmid19028702en_HK
dc.identifier.scopuseid_2-s2.0-58949100355en_HK
dc.identifier.hkuros166975en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-58949100355&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume30en_HK
dc.identifier.issue1en_HK
dc.identifier.spage131en_HK
dc.identifier.epage140en_HK
dc.identifier.isiWOS:000262718300018-
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.scopusauthoridWong, ESY=23101622300en_HK
dc.identifier.scopusauthoridChan, HY=26024081600en_HK
dc.identifier.scopusauthoridIp, PPC=7003622683en_HK
dc.identifier.scopusauthoridNgan, HYS=34571944100en_HK
dc.identifier.scopusauthoridCheung, ANY=54927484100en_HK

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