Phospholipase C-gamma 1 (PLC-gamma l) mediates signals from various extracellular origins to evoke cellular events such as mitogenesis. Previously, we reported that PLC-gamma 1 was highly expressed in colorectal cancer and familial adenomatous polyposis, suggesting that PLC-gamma 1 might be oncogenic. In this study, we have established rat 3Y1 fibroblasts that overexpress whole PLC-gamma 1 and src homology 2 (SH2)-SH2-SH3 domain of PLC-gamma 1. These cells showed a transformed phenotype and were tumorigenic when transplanted into nude mice. These results indicate that overexpression of PLC-gamma 1 could transform rat fibroblasts, and the transformation is mediated by SH2-SH2-SH3 domain of PLC-gamma 1