Transgenic expression of walleye dermal sarcoma virus rv-cyclin gene in zebrafish and its suppressive effect on liver tumor development after carcinogen treatment.
A retrovirus homologue gene of cellular cyclin D₁, 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.
Zhan
Huiqing
H
Department of Biological Sciences, National University of Singapore, Singapore, Singapore 117543.
Spitsbergen
Jan M
JM
Qing
Wei
W
Wu
Yi Lian
YL
Paul
Thomas A
TA
Casey
James W
JW
Her
Guor Muor
GM
Gong
Zhiyuan
Z
D018248:Adenoma, Liver Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018281:Cholangiocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D030283:Epsilonretrovirus / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D005814:Genes, Viral; D008099:Liver / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics* / Q000378:metabolism
D014764:Viral Proteins