Establishment of transgenic zebrafish model for liver cancer studies

Abstract

<P>WE USED ZEBRAFISH AS AN ANIMAL MODEL FOR LIVER CANCER RESEARCH. SEVERAL STABLE TRANSGENIC ZEBRAFISH LINES WERE SUCCESSFULLY GENERATED TO EXPRESS SEVERAL ONCOGENES SPECIFICALLY IN THE LIVER/SKIN USING THE GAL4/UAS SYSTEM. THESE ONCOGENES INCLUDED C-MYC, HEPATITIS B VIRUS X GENE, WOODCHUCK HEPATITIS VIRUS X GENE, WALLEYE DERMAL SARCOMA VIRUS ORFA GENE (WORFA). OBVIOUS NEOPLASIA PHENOTYPES WERE NOT OBSERVED IN THESE TRANSGENIC FISH TILL 1.5 YEARS OLD. THIS MIGHT BE DUE TO THE WEAK EXPRESSION OF ONCOGENE AND/OR INSUFFICIENT TUMORIGENESIS CAPABILITY FROM SINGLE ONCOGENE EXPRESSION. TRANSGENIC FISH LINES WERE THEN TREATED BY CARCINOGEN DMBA TO INVESTIGATE THE CANCER SUSCEPTIBILITY AND CARCINOGENESIS IN THE LIVER. FOR THE TRANSGENIC LINE EXPRESSING WORFA GENE, WE FOUND THAT THE TRANSGENIC FISH EXPRESSING WORFA GENE WAS MORE RESISTANT TO DMBA AND LESS MALIGNANT LIVER CANCERS WERE OBSERVED IN THESE FISH COMPARED WITH THE SIBLING CONTROL. THIS INTERESTING OBSERVATION IN THIS TRANSGENIC FISH M