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Aberrant Expression of the p53-Inducible Antiproliferative Gene BTG2 in Hepatocellular Carcinoma is Associated with Overexpression of the Cell Cycle-Related Proteins

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Abstract

We previously reported that the abnormal BTG2 expression was related to genesis/development of hepatocellular carcinoma (HCC). The aim of this study was to evaluate the BTG2 expression in HCC compared with p53, cyclin D1, and cyclin E. For this purpose, modified diethylnitrosamine (DEN)-induced primary HCC rat model was established. Target proteins and mRNAs were measured by western blot and RT-PCR/northern blot, respectively. In rat liver, expression of BTG2 and other proteins was determined by western blot, and BTG2 mRNA in HCC/normal tissues was detected by high-flux tissue microarray (TMA) and in situ hybridization (ISH). BTG2 mRNA/protein expression was increased in fetal liver, 7701, and LO2 cell lines but decreased in HepG2 cells. BTG2/p53 were expressed early after DEN treatment, peaked at 5 weeks and decreased gradually thereafter. Cyclin-D1/Cyclin-E expression increased significantly with the tumor progression. BTG2 mRNA was expressed in 71.19% HCC by ISH and correlated with differentiation. Expression of p53/cyclin D1/cyclin E was positive in 82.35/94.12/76.47% BTG2 mRNA-negative tissues, respectively. BTG2 protein expression was lost in 32.2% (19/59) HCC tissues, and the mRNA/protein expression correlated significantly with the increasing tumor grade (P < 0.05). In conclusion, BTG2 expression is commonly impaired in HCC which may be a factor involved in deregulation of cyclin-D1/cyclin-E expression during hepatocarcinogenesis.

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Acknowledgments

We thank the Chinese National Natural Science Foundation (Grants #30973457, #30901764) and the Academic Foundation for Authors of National Excellent Doctoral Dissertation of China (Award # 200261) for financial support.

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Authors and Affiliations

  1. Cancer Center, Institute of Surgical Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, China

    Zhimin Zhang, Chuan Chen, Ge Wang, Zhixiang Yang, Jinlu San, Jijun Zheng, Qiong Li, Xizhong Luo, Qing Hu, Zengpeng Li & Dong Wang

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  1. Zhimin Zhang
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  2. Chuan Chen
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  3. Ge Wang
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  4. Zhixiang Yang
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  8. Xizhong Luo
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  9. Qing Hu
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  10. Zengpeng Li
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  11. Dong Wang
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Correspondence to Ge Wang.

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Zhimin Zhang and Chuan Chen contributed equally to this study as co-first authors.

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Zhang, Z., Chen, C., Wang, G. et al. Aberrant Expression of the p53-Inducible Antiproliferative Gene BTG2 in Hepatocellular Carcinoma is Associated with Overexpression of the Cell Cycle-Related Proteins. Cell Biochem Biophys 61, 83–91 (2011). https://doi.org/10.1007/s12013-011-9164-x

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  • DOI: https://doi.org/10.1007/s12013-011-9164-x

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