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 implicated as a key enzyme in signal transduction. We examined the expression of an isozyme of PLC, PLC,-δ, in rat colon neoplasms induced by methylazoxymethanol (MAM) acetate. Large-bowel neoplasms were observed in five of 10 rats given MAM acetate (25 mg/kg body weight, by interperitoneal injection at 6 and 7 wk of age) 40 wk after treatment. Expression of PLC-δ in the neoplasms was not detected by northern blot analysis, and a low level of expression was detected by immunoblot analysis, although PLC-δ expression was apparent in the non-neoplastic colon mucosae of MAM acetate-treated rats as well as in the colon mucosae of control rats. Furthermore, analysis by reverse transcriptase-polymerase chain reaction revealed that the ratio of the expression of PLC-δ to that of β-action in the neoplasms was significantly lower than the ratios in the non-neoplastic colon mucosae of carcinogen-treated and control rats (P<0.01) However, the ornithine decarboxylase (ODC) activity in the neoplsms was significantly greater than that of the non-neoplastic and control mucosae (P<0.001). The differences in the levels of PLC-δ expression in neoplastic and non-neoplastic tissues and the inverse correlation of PLC-δ expression with ODC activity may suggest that PLC-δ has little effect on the PLC-mediated mitogenic signaling system, at least in MAM acetate-induced colon neoplasms in rats.