OVEREXPRESSION OF PHOSPHOLIPASE C-GAMMA-1 IN RAT 3Y1 FIBROBLAST CELLSLEADS TO MALIGNANT TRANSFORMATION

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