TGFBR3 Co-Downregulated With GATA3 Is Associated With Methylation of the GATA3 Gene in Bladder Urothelial Carcinoma

Authors

  • Xiao-Long Liu,

    1. Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, China
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    • Xiao-Long Liu and Bo-Xin Xue contributed equally to this work.

  • Bo-Xin Xue,

    1. Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, China
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    • Xiao-Long Liu and Bo-Xin Xue contributed equally to this work.

  • Zhe Lei,

    1. Soochow University Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, Suzhou, China
    2. Suzhou Key Laboratory for Molecular Cancer Genetics, Suzhou, China
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  • Dong-Rong Yang,

    1. Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, China
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  • Qing-Chuan Zhang,

    1. Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, China
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  • Yu-Xi Shan,

    Corresponding author
    1. Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, China
    • Correspondence to: Yu-Xi Shan, Department of Urology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou 215004, China. E-mail: shanyuxi1002@126.com or Hong-Tao Zhang, PhD, Soochow University Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, 199 Ren'ai Road, Sino-Singapore Industrial Park, Suzhou 215123, China. E-mail: htzhang@suda.edu.cn

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  • Hong-Tao Zhang

    Corresponding author
    1. Soochow University Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, Suzhou, China
    2. Suzhou Key Laboratory for Molecular Cancer Genetics, Suzhou, China
    • Correspondence to: Yu-Xi Shan, Department of Urology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou 215004, China. E-mail: shanyuxi1002@126.com or Hong-Tao Zhang, PhD, Soochow University Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, 199 Ren'ai Road, Sino-Singapore Industrial Park, Suzhou 215123, China. E-mail: htzhang@suda.edu.cn

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ABSTRACT

Bladder urothelial carcinoma (BUC) accounts for ∼90% of all cases of bladder cancer. Reduced expression of TGFBR3 has been frequently observed in several types of human cancers. However, little is known about whether expression of TGFBR3 reduced in BUC and the underlying mechanisms. In the present study, we performed quantitative real-time PCR to examine the mRNA expression of TGFBR3 and GATA3, and bisulfite genomic sequencing to evaluate the methylation status in TGFBR3 and GATA3 promoter regions in fresh tumor and the corresponding paracarcinoma tissues from 29 patients with BUC. As a result, the expression of TGFBR3 and GATA3, a transcriptional factor of the TGFBR3 gene, were found to be co-downregulated in BUC. Moreover, our findings indicated that GATA3 promoter methylation was one of the reasons for silencing of GATA3 and TGFBR3 in BUC, albeit TGFBR3 methylation and mutation were not associated with reduced expression of TGFBR3 mRNA in BUC. In summary, our findings suggest that methylation in the GATA3 promoter region may inhibit the expression of GATA3 mRNA, which leads to the reduced expression of TGFBR3 mRNA in BUC. Anat Rec, 296:1717–1723, 2013. © 2013 Wiley Periodicals, Inc.

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