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Transgenic Expression of Walleye Dermal Sarcoma Virus rv-cyclin Gene in Zebrafish and Its Suppressive Effect on Liver Tumor Development After Carcinogen Treatment

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Abstract

A retrovirus homologue gene of cellular cyclin D 1 , walleye dermal sarcoma virus rv-cyclin gene (orf A or rv-cyclin), was expressed in the livers of zebrafish under the control of liver fatty acid-binding protein (lfabp) promoter. To prevent possible fatality caused by overexpression of the oncogene, the GAL4/upstream activation sequence (GAL4/UAS) system was used to maintain the transgenic lines. Thus, both GAL4-activator [Tg(lfabp:GAL4)] and UAS-effector [Tg(UAS:rvcyclin)] lines were generated, and the rv-cyclin gene was activated in the liver after crossing these two lines. Since no obvious neoplasia phenotypes were observed in the double-transgenic line, cancer susceptibility of the transgenic fish expressing rv-cyclin was tested by carcinogen treatment. Unexpectedly, transgenic fish expressing rv-cyclin gene (rvcyclin+) were more resistant to the carcinogen than siblings not expressing this gene (rvcyclin–). Lower incidences of multiple and malignant liver tumors were observed in rvcyclin+ than in rvcyclin– fish, and the liver tumors in the rvcyclin+ group appeared later and were less malignant. These results suggest that expression of rv-cyclin protects the fish liver from carcinogen damage and delays onset of malignancy. These findings indicate that transgenic fish models are powerful systems for investigating mechanisms of inhibition and regression of liver tumors.

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Acknowledgments

Our research was supported by grants from the Biomedical Research Council of Singapore. The research of Jan Spitsbergen was supported by U.S. Public Health Service grants through the National Institute of Environmental Health Sciences ES013124, ES03850, and ES00210. She received additional support from the John Fryer Salmon Disease Laboratory in the Department of Microbiology at Oregon State University. We thank Dr. Jose A. Campos-Ortega for providing the pBlueScript (KS+)-GAL4 and pBlueScript (KS+)-UAS plasmids.

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Authors and Affiliations

  1. Department of Biological Sciences, National University of Singapore, Singapore, Singapore, 117543

    Huiqing Zhan, Wei Qing, Yi Lian Wu & Zhiyuan Gong

  2. Marine and Freshwater Biomedical Sciences Center and Department of Microbiology, Oregon State University, Corvallis, OR, USA

    Jan M. Spitsbergen

  3. Department of Microbiology and Immunology, Cornell University, Ithaca, NY, USA

    Thomas A. Paul & James W. Casey

  4. Institute of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, Taiwan

    Guor Muor Her

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  1. Huiqing Zhan
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  2. Jan M. Spitsbergen
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  3. Wei Qing
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Correspondence to Zhiyuan Gong.

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Zhan, H., Spitsbergen, J.M., Qing, W. et al. Transgenic Expression of Walleye Dermal Sarcoma Virus rv-cyclin Gene in Zebrafish and Its Suppressive Effect on Liver Tumor Development After Carcinogen Treatment. Mar Biotechnol 12, 640–649 (2010). https://doi.org/10.1007/s10126-009-9251-9

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  • DOI: https://doi.org/10.1007/s10126-009-9251-9

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