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Article: Over-expression of FOXM1 transcription factor is associated with cervical cancer progression and pathogenesis

TitleOver-expression of FOXM1 transcription factor is associated with cervical cancer progression and pathogenesis
Authors
KeywordsCell proliferation
Cervical cancer
FOXM1
Immunohistochemistry
Issue Date2008
PublisherJohn Wiley & Sons. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/1130
Citation
Journal Of Pathology, 2008, v. 215 n. 3, p. 245-252 How to Cite?
Abstract
The Forkhead Box M1 (FOXM1) transcription factor plays a crucial role in regulating expression of cell cycle genes which are essentially involved in cell proliferation, differentiation and transformation. Recent studies have reported that aberrant expression of FOXM1 in a variety of human cancers is associated with their aggressive behaviour. However, the functional significance of FOXM1 in human cervical cancer is not known. We have shown that FOXM1 was significantly over-expressed in cervical squamous cell carcinoma (SCC) compared to normal cervical epithelium immunohistochemically (p < 0.001). In addition, intratumoural FOXM1 positivity was increased in cervical intraepithelial neoplasia (CIN) and carcinoma, compared with that in normal epithelium, indicating that FOXM1 is involved in tumour progression. Indeed, this is supported by clinicopathological analysis that the overexpression of FOXM1 was significantly associated with tumour late stage (p = 0.012) and cell proliferation marker, Ki67 (p < 0.001). Functionally, enforced expression of FOXM1c in FOXM1-deficient cervical cancer cells (C33A) remarkably enhanced cell proliferation and anchorage-independent growth ability. Conversely, depletion of FOXM1 by RNA interference in FOXM1-over-expressing cervical cancer cells (SiHa) caused significant inhibition on cell proliferation and anchorage-independent growth ability on soft agar. This inhibitory phenomenon was associated with the reduced expressions of cyclin B1, cyclinD1 and cdc25B but increased expression of p27 Kip1 and p21 Cip1. Our findings suggest a role for FOXM1 in the development and pathogenesis of human cervical SCC. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/58268
ISSN
2013 Impact Factor: 7.330
ISI Accession Number ID
References

 

Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. Queen Mary Hospital Hong Kong
DC FieldValueLanguage
dc.contributor.authorChan, DWen_HK
dc.contributor.authorYu, SYMen_HK
dc.contributor.authorChiu, PMen_HK
dc.contributor.authorYao, KMen_HK
dc.contributor.authorLiu, VWSen_HK
dc.contributor.authorCheung, ANYen_HK
dc.contributor.authorNgan, HYSen_HK
dc.date.accessioned2010-05-31T03:27:07Z-
dc.date.available2010-05-31T03:27:07Z-
dc.date.issued2008en_HK
dc.identifier.citationJournal Of Pathology, 2008, v. 215 n. 3, p. 245-252en_HK
dc.identifier.issn0022-3417en_HK
dc.identifier.urihttp://hdl.handle.net/10722/58268-
dc.description.abstractThe Forkhead Box M1 (FOXM1) transcription factor plays a crucial role in regulating expression of cell cycle genes which are essentially involved in cell proliferation, differentiation and transformation. Recent studies have reported that aberrant expression of FOXM1 in a variety of human cancers is associated with their aggressive behaviour. However, the functional significance of FOXM1 in human cervical cancer is not known. We have shown that FOXM1 was significantly over-expressed in cervical squamous cell carcinoma (SCC) compared to normal cervical epithelium immunohistochemically (p < 0.001). In addition, intratumoural FOXM1 positivity was increased in cervical intraepithelial neoplasia (CIN) and carcinoma, compared with that in normal epithelium, indicating that FOXM1 is involved in tumour progression. Indeed, this is supported by clinicopathological analysis that the overexpression of FOXM1 was significantly associated with tumour late stage (p = 0.012) and cell proliferation marker, Ki67 (p < 0.001). Functionally, enforced expression of FOXM1c in FOXM1-deficient cervical cancer cells (C33A) remarkably enhanced cell proliferation and anchorage-independent growth ability. Conversely, depletion of FOXM1 by RNA interference in FOXM1-over-expressing cervical cancer cells (SiHa) caused significant inhibition on cell proliferation and anchorage-independent growth ability on soft agar. This inhibitory phenomenon was associated with the reduced expressions of cyclin B1, cyclinD1 and cdc25B but increased expression of p27 Kip1 and p21 Cip1. Our findings suggest a role for FOXM1 in the development and pathogenesis of human cervical SCC. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.en_HK
dc.languageengen_HK
dc.publisherJohn Wiley & Sons. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/1130en_HK
dc.relation.ispartofJournal of Pathologyen_HK
dc.rightsJournal of Pathology. Copyright © John Wiley & Sons Ltd.en_HK
dc.subjectCell proliferationen_HK
dc.subjectCervical canceren_HK
dc.subjectFOXM1en_HK
dc.subjectImmunohistochemistryen_HK
dc.subject.meshBiological Markers - analysisen_HK
dc.subject.meshBlotting, Western - methodsen_HK
dc.subject.meshCarcinoma, Squamous Cell - geneticsen_HK
dc.subject.meshCell Cycle Proteins - analysis - geneticsen_HK
dc.subject.meshCell Proliferationen_HK
dc.subject.meshCervix Uteri - chemistry - metabolismen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshForkhead Transcription Factors - analysis - geneticsen_HK
dc.subject.meshGene Expressionen_HK
dc.subject.meshGene Expression Regulation, Neoplasticen_HK
dc.subject.meshHumansen_HK
dc.subject.meshImmunohistochemistryen_HK
dc.subject.meshMiddle Ageden_HK
dc.subject.meshNeoplasm Stagingen_HK
dc.subject.meshStatistics, Nonparametricen_HK
dc.subject.meshTumor Markers, Biological - analysisen_HK
dc.subject.meshUterine Cervical Neoplasms - geneticsen_HK
dc.titleOver-expression of FOXM1 transcription factor is associated with cervical cancer progression and pathogenesisen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-3417&volume=215 &issue=3&spage=245&epage=252&date=2008&atitle=Over-expression+of+FOXM1+transcription+factor+is+associated+with+cervical+cancer+progression+and+pathogenesisen_HK
dc.identifier.emailChan, DW: dwchan@hku.hken_HK
dc.identifier.emailYao, KM: kmyao@hku.hken_HK
dc.identifier.emailLiu, VWS: vwsliu@hkusua.hku.hken_HK
dc.identifier.emailCheung, ANY: anycheun@hkucc.hku.hken_HK
dc.identifier.emailNgan, HYS: hysngan@hkucc.hku.hken_HK
dc.identifier.authorityChan, DW=rp00543en_HK
dc.identifier.authorityYao, KM=rp00344en_HK
dc.identifier.authorityLiu, VWS=rp00341en_HK
dc.identifier.authorityCheung, ANY=rp00542en_HK
dc.identifier.authorityNgan, HYS=rp00346en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/path.2355en_HK
dc.identifier.pmid18464245en_HK
dc.identifier.scopuseid_2-s2.0-46849097424en_HK
dc.identifier.hkuros144697en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-46849097424&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume215en_HK
dc.identifier.issue3en_HK
dc.identifier.spage245en_HK
dc.identifier.epage252en_HK
dc.identifier.eissn1096-9896-
dc.identifier.isiWOS:000257332500005-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridChan, DW=26533900600en_HK
dc.identifier.scopusauthoridYu, SYM=24463692000en_HK
dc.identifier.scopusauthoridChiu, PM=7103182596en_HK
dc.identifier.scopusauthoridYao, KM=7403234578en_HK
dc.identifier.scopusauthoridLiu, VWS=7006405113en_HK
dc.identifier.scopusauthoridCheung, ANY=54927484100en_HK
dc.identifier.scopusauthoridNgan, HYS=34571944100en_HK

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