Zou Lin, Zhang Penghui, Luo Chunli, Tu Zhiguang
Faculty of Laboratory Medicine at Chongqing University of Medical Sciences, Key Laboratory of Laboratory Medical Diagnosis of Education Ministry, Chongqing, China.
Urology. 2006 Jun;67(6):1335-40. doi: 10.1016/j.urology.2005.12.029.
To study the effects and possible mechanisms of mitosis arrest deficiency 1 (Mad1), the heterodimerizer of Max and a transcriptional repressor, on cell proliferation of bladder cancer in vitro and in vivo.
Combining methyl thiazolyl tetrazolium (MTT) assay, flow cytometry, luciferase assay, telomeric repeat amplification protocol-enzyme-linked immunosorbent assay, real-time reverse transcriptase polymerase chain reaction, experimental animal models, and other assays, we detected the alterations of cell proliferation, cell cycle, promoter activity and expression of human telomerase reverse transcriptase (hTERT), and telomerase activity in different treated bladder cells and xenograft tissues.
Mad1 inhibited cell proliferation, increased G0/G1 accumulation in cell cycle distribution, decreased the transcription and expression of hTERT, and reduced telomerase activity compared with controls in T24 and EJ cells. Mad1 also arrested tumor growth and downregulated hTERT expression and telomerase activity in bladder cancer xenograft BALB/c nude mice.
Mad1 inhibited the proliferation of human bladder cancer cells by inhibiting hTERT transcription and telomerase activity. Mad1 could be a potentially useful candidate for inhibition of bladder cancer growth.
研究Max的异二聚体化蛋白及转录抑制因子有丝分裂阻滞缺陷蛋白1（Mad1）在体外和体内对膀胱癌细胞增殖的影响及可能机制。
结合甲基噻唑基四氮唑蓝（MTT）法、流式细胞术、荧光素酶报告基因检测、端粒重复序列扩增法-酶联免疫吸附测定、实时逆转录聚合酶链反应、实验动物模型等检测方法，我们检测了不同处理的膀胱癌细胞和异种移植组织中细胞增殖、细胞周期、启动子活性以及人端粒酶逆转录酶（hTERT）的表达和端粒酶活性的变化。
与对照相比，在T24和EJ细胞中，Mad1抑制细胞增殖，增加细胞周期分布中G0/G1期的积累，降低hTERT的转录和表达，并降低端粒酶活性。Mad1还能抑制膀胱癌异种移植BALB/c裸鼠的肿瘤生长，并下调hTERT表达和端粒酶活性。
Mad1通过抑制hTERT转录和端粒酶活性来抑制人膀胱癌细胞的增殖。Mad1可能是抑制膀胱癌生长的潜在有用候选物。
