Synergistic effect of Myc and xmrk oncogenes in transgenic zebrafish survival and liver tumorigenesis.

(A,B) Survival curve (A) and gross morphology (B) of oncogene transgenic zebrafish following doxycycline induction at the juvenile stage (starting from 21 dpf). (C) Survival curve of oncogene transgenic zebrafish following doxycycline induction at the adult stage (starting from 3.5 mpf). (D) Gross observation of liver phenotype (left) and histological sections of livers stained by hematoxylin and eosin dyes (right). Abbreviations: X,xmrk; M,Myc; D, doxycycline treatment.

Suppression of growth of oncogenic livers in Myc/xmrk double transgenic larvae by Pkm2 activation.

10 µg/ml TEPP-46 was used to treat zebrafish larvae from 4 dpf for 96 hours and 2D liver size was measured by using ImageJ (1.49J) and cell proliferation on cryosections were examined by immune-staining of PCNA. (A,B) Changes of 2D liver size. Representative images from each group are shown in (A) and quantification of 2D liver size is presented in (B). (C,D) Immunostaining of PCNA for cell proliferation. Representative images in the liver area from each experimental group are shown in (A) and quantification of PCNA positive cells as percentage of liver cells is presented in (B). Group designations: X for xmrk, M for Myc, and T for TEPP-46. + and—indicate presence and absence respectively. All groups also received 30 µg/ml doxycycline in the experimental duration (4–8 dpf). Statistical significance was examined by unpaired student t test. *P<0.05; **P<0.01; ****P<0.0001.