Liu Dongye, Zhang Zhe, Kong Chui-ze
Department of Urology, First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang, 110001, China.
Tumour Biol. 2013 Apr;34(2):1131-8. doi: 10.1007/s13277-013-0654-x. Epub 2013 Jan 17.
The forkhead box M1 (FOXM1) transcription factor plays crucial roles in regulating the proliferation, differentiation, and transformation of cells. Overexpression of FOXM1 is associated with a variety of aggressive solid carcinomas, including bladder cancer. However, the precise role and molecular mechanism responsible for the aggressive action of FOXM1 in bladder cancer remain unclear. Real-time quantitative PCR, Western blot and immunohistochemistry were used to explore FoxM1 expression in bladder cancer cell lines, primary bladder cancer clinical specimens and normal bladder tissues. FoxM1 expression was knocked down by small interfering RNA (siRNA) in T24 cells; proliferation, migration and invasion were assayed. FoxM1 expression was up-regulated in the majority of the bladder cancer tissue specimens at both mRNA and protein levels. Immunohistochemistry analysis showed that FoxM1 expression was significantly correlated with TNM stage and histological grade, metastasis. Experimentally, we found that down-regulation of FoxM1 inhibited cell proliferation, migration and invasion. These results suggested that FOXM1 up-regulation was associated with poor prognosis in bladder cancer, and therefore it might act as a prognostic marker and a new potential target for bladder cancer treatment.
叉头框M1（FOXM1）转录因子在调节细胞增殖、分化和转化过程中发挥着关键作用。FOXM1的过表达与包括膀胱癌在内的多种侵袭性实体癌相关。然而，FOXM1在膀胱癌中发挥侵袭作用的确切作用和分子机制仍不清楚。采用实时定量PCR、蛋白质印迹法和免疫组织化学法，探究FoxM1在膀胱癌细胞系、原发性膀胱癌临床标本及正常膀胱组织中的表达情况。在T24细胞中，利用小干扰RNA（siRNA）敲低FoxM1表达，检测细胞增殖、迁移和侵袭能力。在大多数膀胱癌组织标本中，FoxM1在mRNA和蛋白质水平均呈上调表达。免疫组织化学分析表明，FoxM1表达与TNM分期、组织学分级及转移显著相关。实验发现，下调FoxM1可抑制细胞增殖、迁移和侵袭。这些结果提示，FOXM1上调与膀胱癌预后不良相关，因此它可能作为膀胱癌治疗的预后标志物和新的潜在靶点。
