Transgenic expression of Walleye dermal sarcoma virus rv-cyclin gene in zebrafish and its protective 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 over-expression of the oncogene, the 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 neoplasial 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+) seemed to be more resistant to the carcinogen than were 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 less severe. These results suggest that expression of
rv-cyclin protects the fish liver from carcinogen damage and delays onset of malignancy.
This observation—from a transgenic fish model—may be relevant to studies of liver-cancer
inhibition and regression.Keywords: Transgenic fish, Carcinogen, Liver neoplasia, Tumor regression, Walleye dermal sarcoma virus rv-cyclin geneKeywords: Transgenic fish, Carcinogen, Liver neoplasia, Tumor regression, Walleye dermal sarcoma virus rv-cyclin gen