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Dickkopf-3/REIC functions as a suppressor gene of tumor growth

Oncogene volume 23, pages 9183–9189 (2004)Cite this article

Abstract

To identify putative tumor suppressor genes in hepatocarcinogenesis, we combined the representational difference analysis and reverse northern blot identifying downregulated genes in human hepatoma tissues. One of them was Dkk-3/REIC. Dkk-3/REIC was downregulated in 11 out of the 20 human hepatoma tissues as compared to their counterparts of noncancerous liver tissues by northern blot analysis. It was also downregulated in 29 out of 48 human cancer samples including the kidney, urinary bladder, prostate, pancreas and lung cancers. Its gene product, Dkk-3/REIC, was found to be N-glycosylated and have two isoforms, the 55 kDa in the cytosol and 50 kDa secreted in the medium. Ectopic expression of Dkk-3/REIC in HeLa, Hep3B and Huh 7 cells led to suppression of cell growth, which was primarily attributable to induction of cell apoptosis. The suppression phenomenon was found to be cell-type related (most prominent in HeLa and least in Hep3B cells) and cell-density dependent (attenuated as the cell density increased). Transduction of Dkk-3/REIC into HeLa and Hep3B cells caused suppression on colony formation in vitro and reduced tumor growth rate in inoculated athymic nude mice. In conclusion, these data indicate that Dkk-3/REIC functions as a suppressor for human tumor growth.

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Acknowledgements

The authors are grateful to Miss Su-Chen Ji for her expertise in graph drawing, and to Miss Jing-Yu Yeh and Mr Hsio-Cheng Chang for their excellent technique assistance. This work was supported in part by a grant from Chang Gung Memorial Hospital and a grant from National Science Council, Taiwan.

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Authors and Affiliations

  1. Liver Research Unit, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan

    Sen-Yung Hsieh, Pei-Shan Hsieh, Cheng-Tang Chiu & Wai-Ying Chen

  2. Department of Microbiology and Immunology, Chang Gung University School of Medicine, Tao-Yuan, 333, Taiwan

    Sen-Yung Hsieh

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  1. Sen-Yung Hsieh
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  2. Pei-Shan Hsieh
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Correspondence to Sen-Yung Hsieh.

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Hsieh, SY., Hsieh, PS., Chiu, CT. et al. Dickkopf-3/REIC functions as a suppressor gene of tumor growth. Oncogene 23, 9183–9189 (2004). https://doi.org/10.1038/sj.onc.1208138

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