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

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...

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Published in:	The Journal of pathology Vol. 215; no. 3; pp. 245 - 252
Main Authors:	Chan, DW, Yu, SYM, Chiu, PM, Yao, KM, Liu, VWS, Cheung, ANY, Ngan, HYS
Format:	Journal Article
Language:	English
Published:	Chichester, UK John Wiley & Sons, Ltd 01-07-2008
Subjects:	Biomarkers - analysis Biomarkers, Tumor - analysis Blotting, Western - methods Carcinoma, Squamous Cell - genetics Cell Cycle Proteins - analysis Cell Cycle Proteins - genetics Cell Proliferation cervical cancer Cervix Uteri - chemistry Cervix Uteri - metabolism Female Forkhead Box Protein M1 Forkhead Transcription Factors - analysis Forkhead Transcription Factors - genetics FOXM1 Gene Expression Gene Expression Regulation, Neoplastic Humans Immunohistochemistry Middle Aged Neoplasm Staging Statistics, Nonparametric Uterine Cervical Neoplasms - genetics
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Summary:	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 p27Kip¹ and p21Cip¹. 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.
Bibliography:	http://dx.doi.org/10.1002/path.2355 istex:7D28E4042C6A78AE408DA022A9EBE4C760D269AE ark:/67375/WNG-WWNDSS6D-R ArticleID:PATH2355 No conflicts of interest were declared. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-3417 1096-9896
DOI:	10.1002/path.2355