Src kinase Induces Tumor Formation in the cSRC C57BL/6 Mouse

We developed the c-SRC transgenic mouse in the C57BL/6 strain to address the issue of carcinogenesis in cells with high levels of Src expression. The transgene was constructed with the human c-SRC gene downstream of the mouse metallothionein promoter to create zinc inducible gene expression. In these C57BL/6 mice, Src protein was increased in a number of tissues both with and without zinc induction, but most highly in the liver. Src expression was inducible with zinc, but typically zinc induction was unnecessary. No additional carcinogenic agent was administered. After 20 months, mice were assessed for tumor development in the liver and GI tract, as well as other organs. 15% of c-Src transgenic mice developed liver tumors while no wild type mice developed tumors. We performed microarray analysis on the livers of wild type and transgenic mice to determine the possible genes downstream of Src that might be involved in carcinogenesis. Microarray runs of Wild Type liver sample #3 and c-SRC transgenic liver sample #2 both gave very low signals, and were not included in the final analysis.