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

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TitleOver-expression of FOXM1 transcription factor is associated with cervical cancer progression and pathogenesis
AuthorsChan, DW1
Yu, SYM1
Chiu, PM1
Yao, KM1
Liu, VWS1
Cheung, ANY1
Ngan, HYS1 2
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
CitationJournal Of Pathology, 2008, v. 215 n. 3, p. 245-252 [How to Cite?]
DOI: http://dx.doi.org/10.1002/path.2355
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.
ISSN0022-3417
2011 Impact Factor: 6.318
2011 SCImago Journal Rankings: 0.946
DOIhttp://dx.doi.org/10.1002/path.2355
ISI Accession Number IDWOS:000257332500005
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorChan, DW
dc.contributor.authorYu, SYM
dc.contributor.authorChiu, PM
dc.contributor.authorYao, KM
dc.contributor.authorLiu, VWS
dc.contributor.authorCheung, ANY
dc.contributor.authorNgan, HYS
dc.date.accessioned2010-05-31T03:27:07Z
dc.date.available2010-05-31T03:27:07Z
dc.date.issued2008
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.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationJournal Of Pathology, 2008, v. 215 n. 3, p. 245-252 [How to Cite?]
DOI: http://dx.doi.org/10.1002/path.2355
dc.identifier.doihttp://dx.doi.org/10.1002/path.2355
dc.identifier.epage252
dc.identifier.hkuros144697
dc.identifier.isiWOS:000257332500005
dc.identifier.issn0022-3417
2011 Impact Factor: 6.318
2011 SCImago Journal Rankings: 0.946
dc.identifier.issue3
dc.identifier.openurl
dc.identifier.pmid18464245
dc.identifier.scopuseid_2-s2.0-46849097424
dc.identifier.spage245
dc.identifier.urihttp://hdl.handle.net/10722/58268
dc.identifier.volume215
dc.languageeng
dc.publisherJohn Wiley & Sons. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/1130
dc.publisher.placeUnited Kingdom
dc.relation.ispartofJournal of Pathology
dc.relation.referencesReferences in Scopus
dc.rightsJournal of Pathology. Copyright © John Wiley & Sons Ltd.
dc.subject.meshBiological Markers - analysis
dc.subject.meshBlotting, Western - methods
dc.subject.meshCarcinoma, Squamous Cell - genetics
dc.subject.meshCell Cycle Proteins - analysis - genetics
dc.subject.meshCell Proliferation
dc.subject.meshCervix Uteri - chemistry - metabolism
dc.subject.meshFemale
dc.subject.meshForkhead Transcription Factors - analysis - genetics
dc.subject.meshGene Expression
dc.subject.meshGene Expression Regulation, Neoplastic
dc.subject.meshHumans
dc.subject.meshImmunohistochemistry
dc.subject.meshMiddle Aged
dc.subject.meshNeoplasm Staging
dc.subject.meshStatistics, Nonparametric
dc.subject.meshTumor Markers, Biological - analysis
dc.subject.meshUterine Cervical Neoplasms - genetics
dc.subjectCell proliferation
dc.subjectCervical cancer
dc.subjectFOXM1
dc.subjectImmunohistochemistry
dc.titleOver-expression of FOXM1 transcription factor is associated with cervical cancer progression and pathogenesis
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. Queen Mary Hospital Hong Kong