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Androgen activates PEG10 to promote carcinogenesis in hepatic cancer cells

Oncogene volume 26, pages 5741–5751 (2007)Cite this article

A Retraction to this article was published on 16 June 2011

Abstract

The molecular mechanism of striking higher prevalence of hepatocellular carcinoma (HCC) in male subjects has not yet been fully elucidated. Here, we report that androgen receptor (AR) is differentially expressed in different HCC cell lines. AR agonist dihydrotestosterone (DHT) enhances HCC cell growth and apoptotic resistance. Antagonist flutamide (FLU) blocks the effects of DHT on the HCC cell lines. Paternally expressed gene 10 (PEG10) is expressed in HCC cell lines at substantial high level. Using small interfering RNAs against AR and PEG10 in AR- and PEG10-expressing BEL-7404 hepatoma cells and HuH7 hepatoma cells (HuH7) cells, and AR-transfection technique in AR-lacking and PEG10-expressing HepG2 cells, we have confirmed that through upregulation and activation of PEG10, DHT enhances HCC cell growth and apoptotic resistance. We have further demonstrated that DHT upregulates expression of human telomerase reverse transcriptase (hTERT) in HCC cell lines in a PEG10-dependent manner. Moreover, AR directly interacts in vivo with androgen-responsive elements in the regions of promoter and exon 2 of PEG10 gene in HCC cell lines. DHT promotes the hepatoma formation in vivo nude mice through PEG10 activation. AR antagonists (FLU and valproate) inhibit the hepatoma formation. These findings suggest that PEG10 plays an essential role in hepatocarcinogenesis. The PEG10 inhibition can be a novel approach for therapy of HCC.

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Acknowledgements

This work was supported by National Natural Science Foundation of China (no. 39870674, 30572119, 30030130, 30471509, 30670937). Dr Tan Jinquan is a Chang Jiang Scholar supported by Chang Jiang Scholars Program from Ministry of Education, China and Li Ka Shing Foundation, Hong Kong, China.

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Author notes

  1. X Jie, C Lang, Q Jian, L Chaoqun and Y Dehua: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Immunology, and Laboratory of Allergy and Clinical Immunology, Institute of Allergy and Immune-related Diseases and Medical Research Center, Wuhan University School of Medicine, Wuhan, China

    X Jie, C Lang, Q Jian, J Yanping, X Luokun, Z Qiuping & T Jinquan

  2. The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai, China

    X Jie, L Chaoqun, Y Dehua, S Yi & J Youxin

  3. Department of Infectious Diseases, Ruijin Hospital, Shanghai Second Medical University, Shanghai, China

    L Chaoqun

  4. College of Life Sciences, South China Normal University, Guangzhou, China

    Y Dehua

  5. Department of Pharmacology, Wuhan University School of Medicine, Wuhan, China

    W Hui

  6. Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    G Feili

  7. Department of Immunology, Fourth Military Medical University, Xian, China

    J Boquan

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  1. X Jie
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Correspondence to J Youxin or T Jinquan.

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Jie, X., Lang, C., Jian, Q. et al. Androgen activates PEG10 to promote carcinogenesis in hepatic cancer cells. Oncogene 26, 5741–5751 (2007). https://doi.org/10.1038/sj.onc.1210362

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