Oncotarget

Research Papers:

The C228T mutation of TERT promoter frequently occurs in bladder cancer stem cells and contributes to tumorigenesis of bladder cancer

Chong Li _, Song Wu, Haifeng Wang, Xingang Bi, Zhao Yang, Ying Du, Luyun He, Zhiming Cai, Jiansong Wang and Zusen Fan

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Oncotarget. 2015; 6:19542-19551. https://doi.org/10.18632/oncotarget.4295

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Abstract

Chong Li1,2,*, Song Wu2,*, Haifeng Wang3,*, Xingang Bi4,*, Zhao Yang1,*, Ying Du1, Luyun He1, Zhiming Cai2, Jiansong Wang3, Zusen Fan1

1CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China

2Department of Urology, The Second People’s Hospital of Shenzhen, Shenzhen 518035, China

3Department of Urology, The Second Affiliated Hospital of Kunming Medical College, Kunming 650101, China

4Cancer Institute & Hospital Chinese Academy of Medical Sciences, Beijing 100021, China

*These authors have contributed equally to this work

Correspondence to:

Zusen Fan, e-mail: fanz@moon.ibp.ac.cn

Zhiming Cai, e-mail: caizhiming2000@163.com

Jiansong Wang, e-mail: jiansongwang@yahoo.com

Keywords: bladder cancer stem cells, C228T mutation, telomerase reverse transcriptase (TERT), tumorigenesis

Received: April 10, 2015     Accepted: June 04, 2015     Published: June 17, 2015

ABSTRACT

Bladder cancer is one of the most common malignant tumors worldwide. Bladder cancer stem cells (BCSCs) have been isolated recently but have not been defined yet. Here we sorted BCSCs from bladder tumor tissues or normal bladder stem cells (NBBCs) from adjacent normal bladder tissues. We found that the C228T mutation (chr5, 1, 295, 228 C > T) of TERT promoter frequently occurs in BCSCs, but not exist in NBBCs. Importantly, introducing the C228T mutation in NBBCs causes TERT overexpression and transformation of bladder cancer. Restoration of the C228T mutation to T228C in BCSCs can recover the TERT expression to a basal level and abolish tumor formation. Additionally, the C228T mutation of TERT promoter triggers TERT expression leading to increased telomerase activity. TERT expression levels are consistent with clinical severity and prognosis of bladder cancer.


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