Document Detail


Over-expression of FOXM1 transcription factor is associated with cervical cancer progression and pathogenesis.
MedLine Citation:
PMID:  18464245     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 over-expression 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.
Authors:
D W Chan; S Y M Yu; P M Chiu; K M Yao; V W S Liu; A N Y Cheung; H Y S Ngan
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of pathology     Volume:  215     ISSN:  0022-3417     ISO Abbreviation:  J. Pathol.     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-06-11     Completed Date:  2008-08-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0204634     Medline TA:  J Pathol     Country:  England    
Other Details:
Languages:  eng     Pagination:  245-52     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2008 Pathological Society of Great Britain and Ireland.
Affiliation:
Department of Obstetrics and Gynaecology, LKS Faculty of Medicine, University of Hong Kong, Hong Kong SAR, People's Republic of China.
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MeSH Terms
Descriptor/Qualifier:
Biological Markers / analysis
Blotting, Western / methods
Carcinoma, Squamous Cell / genetics*
Cell Cycle Proteins / analysis,  genetics
Cell Proliferation
Cervix Uteri / chemistry,  metabolism
Female
Forkhead Transcription Factors / analysis,  genetics*
Gene Expression
Gene Expression Regulation, Neoplastic*
Humans
Immunohistochemistry
Middle Aged
Neoplasm Staging
Statistics, Nonparametric
Tumor Markers, Biological / analysis
Uterine Cervical Neoplasms / genetics*
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Cell Cycle Proteins; 0/FOXM1 protein, human; 0/Forkhead Transcription Factors; 0/Tumor Markers, Biological

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