Fibulin-1 is epigenetically down-regulated and related with bladder cancer recurrence

BMC Cancer

Wei Xiao³  Ji Wang²  Heng Li⁴  Ding Xia⁴  Gan Yu⁴  Weimin Yao⁴  Yang Yang⁴  Haibing Xiao⁴  Bin Lang⁵  Xin Ma¹  Xiaolin Guo⁴  Wei Guan⁴  Hua Xu⁴  Jihong Liu⁴  Xu Zhang¹  Zhangqun Ye⁴ 

[1] Department of Urology, PLA General Hospital, Military Postgraduate Medical College, Beijing 100853, China

[2] Department of Urology and Helen-Diller Comprehensive Cancer Center, University of California, San Francisco, California, USA

[3] Translational Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

[4] Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

[5] School of Health Sciences, Macao Polytechnic Institute, Macao, China

关键词: Cancer recurrence;    Tumor suppressor gene;    Promoter hypermethylation;    Bladder cancer;    Fibulin-1;   

Others  :  1121064
DOI  :  10.1186/1471-2407-14-677

 received in 2014-06-02, accepted in 2014-09-10,  发布年份 2014

【 摘 要 】

Background

Bladder cancer is one of the most common cancers worldwide. Fibulin-1, a multi-functional extracellular matrix protein, has been demonstrated to be involved in many kinds of cancers, while its function in bladder cancer remains unclear. So here we investigated the expression and function of fibulin-1 in Bladder cancer.

Methods

We used real-time PCR, Western blot analysis and immunohistochemistry to determine the expression of fibulin-1 in Bladder cancer cells and patient tissues respectively. Methylation-specific PCR and quantitative sequencing were used to examine the methylation status of FBLN1 gene promoter. Eukaryotic expression plasmid and lentiviral vector were used to overexpress fibulin-1 in Bladder cancer cells 5637, HT-1376 to investigate its function in vitro and in vivo.

Results

We identified that fibulin-1 was significantly down-regulated in bladder cancer, and its dysregulation was associated with non-muscle-invasive bladder cancer (NMIBC) grade and recurrence. The promoter region of FBLN1 was generally methylated in bladder cancer cell lines and tissues, further investigation in patient tissues showed that the methylation status was associated with the fibulin-1 expression. Overexpression of fibulin-1 significantly suppressed tumor growth, induced tumor cell apoptosis, decreased cell motility, and inhibited angiogenesis in cultured bladder cancer cells and xenograft tumor in nude mice.

Conclusions

Altogether, our results indicated that fibulin-1 expression is associated with NMIBC grade and recurrence, it is epigenetically down-regulated and functions as a tumor suppressor gene and angiogenesis inhibitor in bladder cancer.

【 授权许可】

   
2014 Xiao et al.; licensee BioMed Central Ltd.

【 图 表 】

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