Mad1 suppresses bladder cancer cell proliferation by inhibiting human telomerase reverse transcriptase transcription and telomerase activity.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Zou
Lin
L
Faculty of Laboratory Medicine at Chongqing University of Medical Sciences, Key Laboratory of Laboratory Medical Diagnosis of Education Ministry, Chongqing, China.
Zhang
Penghui
P
Luo
Chunli
C
Tu
Zhiguang
Z
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000502:physiology*; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology*; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C501384:MAD1L1 protein, human; D009687:Nuclear Proteins; D019098:Telomerase