BTG2 is a tumor suppressor gene upregulated by p53 and PTEN in human bladder carcinoma cells

Ke Hung Tsui, Kun Chun Chiang, Yu Hsiang Lin, Kang Shuo Chang, Tsui Hsia Feng, Horng Heng Juang

研究成果: 雜誌貢獻文章同行評審

35 引文 斯高帕斯(Scopus)

摘要

Although widely deemed as a tumor suppressor gene, the role of B-cell translocation gene 2 (BTG2) in bladder cancer is still inconclusive. We investigated the role and regulatory mechanism of BTG2 in bladder cancer. BTG2 expression in human bladder tissues was determined by RT-qPCR and immunoblotting assays. Expressions of BTG2 and PTEN in bladder carcinoma cells were determined by immunoblotting, RT-qPCR, or reporter assays. The 3H-thymidine incorporation assay, flow cytometry, and the xenograft animal model were used to determine the cell growth. BTG2 expression was lower in human bladder cancer tissues than normal bladder tissues. Highly differentiated bladder cancer cells, RT4, expressed higher BTG2 than the less-differentiated bladder cancer cells, HT1376 and T24. Overexpression of BTG2 in T24 cells inhibited cell growth in vitro and in vivo. Camptothecin and doxorubicin treatments in RT-4 cells or transient overexpression of p53 into p53-mutant HT1376 cells induced p53 and BTG2 expression. Further reporter assays with site-mutation of p53 response element from GGGAAAGTCC to GGAGTCC within BTG2 promoter area showed that p53-induced BTG2 gene expression was dependent on the p53 response element. Ectopic PTEN overexpression in T24 cells blocked the Akt signal pathway which attenuated cell growth via upregualtion of BTG2 gene expression, while reverse effect was found in PTEN-knockdown RT-4 cells. PTEN activity inhibitor (VO-OHpic) treatment decreased BTG2 expression in RT-4 and PTEN-overexpressed T24 cells. Our results suggested that BTG2 functioned as a bladder cancer tumor suppressor gene, and was induced by p53 and PTEN. Modulation of BTG2 expression seems a promising way to treat human bladder cancer.
原文英語
頁(從 - 到)184-195
頁數12
期刊Cancer Medicine
7
發行號1
DOIs
出版狀態已發佈 - 1月 2018
對外發佈

ASJC Scopus subject areas

  • 腫瘤科
  • 放射學、核子醫學和影像學
  • 癌症研究

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