Over-expression of FOXM1 transcription factor is associated with cervical cancer progression and pathogenesis
Over-expression of FOXM1 transcription factor is associated with cervical cancer progression and pathogenesis
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DOI：
10.1002/path.2355
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发表时间：
2008-07-01
影响因子：
7.3
通讯作者：
Ngan, H. Y. S.
中科院分区：
文献类型：
--
作者：
Chan, D. W.;Yu, S. Y. M.;Ngan, H. Y. S.
叉头盒M1 （Forkhead Box M1, FOXM1）转录因子在调控细胞周期基因的表达中起着至关重要的作用，这些基因本质上参与细胞的增殖、分化和转化。最近的研究报道，FOXM1在多种人类癌症中的异常表达与它们的攻击行为有关。然而，FOXM1在人宫颈癌中的功能意义尚不清楚。我们发现，与正常宫颈上皮相比，FOXM1在宫颈鳞状细胞癌（SCC）中显著过表达（p < 0.001）。此外，与正常上皮相比，宫颈上皮内瘤变（CIN）和癌中FOXM1瘤内阳性升高，表明FOXM1参与肿瘤进展。事实上，临床病理分析证实FOXM1的过表达与肿瘤晚期（p = 0.012）和细胞增殖标志物Ki67 （p < 0.001）显著相关。在功能上，FOXM1c在foxm1缺陷宫颈癌细胞（C33A）中的强制表达显著增强了细胞增殖和不依赖于锚定的生长能力。相反，在FOXM1过表达的宫颈癌细胞（SiHa）中，通过RNA干扰去除FOXM1，可显著抑制细胞增殖和软琼脂上不依赖锚定的生长能力。这种抑制现象与cyclin B1、cyclinD1和cdc25B的表达减少而p27（Kip1）和p22（Cip1）的表达增加有关。我们的研究结果提示FOXM1在人宫颈鳞状细胞癌的发展和发病机制中起作用。版权所有2008年英国和爱尔兰病理学会。约翰·威利父子有限公司出版。
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 p22(Cip1). Our findings suggest a role for FOXM1 in the development and pathogenesis of human cervical SCC. Copyright (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.