REDUCED EXPRESSION OF PHOSPHOLIPASE C-DELTA A SIGNAL-TRANSDUCING ENZYME, IN RAT COLON NEOPLASMS INDUCED BY METHYLAZOXYMETHANOL ACETATE

Phospholipase C (PLC), which hydrolyzes phosphoinositides, has been im plicated as a key enzyme in signal transduction. We examined the expre ssion of an isozyme of PLC, PLC-delta, in rat colon neoplasms induced by methylazoxymethanol (MAM) acetate. Large-bower neoplasms were obser ved in five of 10 rats given MAM acetate (25 mg/kg body weight, by int erperitoneal injection at 6 and 7 wk of age) 40 wk after treatment. Ex pression of PLC-delta in the neoplasms was not detected by northern bl ot analysis, and a low level of expression was detected by immunoblot analysis, although PLC-delta expression was apparent in the non-neopla stic colon mucosae of MAM acetate-treated rats as well as in the colon mucosae of control rats. Furthermore, analysis by reverse transcripta se-polymerase chain reaction revealed that the ratio of the expression of PLC-delta to that of beta-actin in the neoplasms was significantly lower than the ratios in the non-neoplastic colon mucosae of carcinog en-treated and control rats (P < 0.01). However, the ornithine decarbo xylase (ODC) activity in the neoplasms was significantly greater than that of the non-neoplastic and control mucosae (P < 0.001). The differ ences in the levels of PLC-delta expression in neoplastic and non-neop lastic tissues and the inverse correlation of PLC-delta expression wit h ODC activity may suggest that PLC-delta has little effect on the PLC -mediated mitogenic signaling system, at least in MAM acetate-induced colon neoplasms in rats. (C) 1994 Wiley-Liss, Inc.