OVEREXPRESSION OF PHOSPHOLIPASE C-GAMMA-1 IN FAMILIAL ADENOMATOUS POLYPOSIS

Abstract

Phosphoinositide-specific phospholipase C (PLC) isozymes occupy a central role in the signal transduction system by regulating various cellular processes including proliferation and differentiation. In the present study, we examined the contents of PLCs in colorectal adenomas, carcinomas, and normal mucosa obtained from 4 familial adenomatous polyposis patients to find out whether this enzyme plays any role in the pathogenesis of adenomas and/or carcinomas in familial adenomatous polyposis. Radioimmunoassay and immunoblot analysis revealed that in contrast to little difference in PLC-beta 1 and PLC-delta 1 content, a considerably higher level of PLC-gamma 1 was detected in 3 of 4 cases for adenoma and in all cases for carcinoma as compared to normal mucosa. The level of PLC-gamma 1 expression increased from normal mucosa to adenoma, and finally to carcinoma progressively. Immunohistochemical findings also confirmed this observation. Likewise, activity of PLC-gamma 1 was considerably higher in adenomas and carcinomas than in normal mucosa. These results suggest that PLC-gamma 1-mediated signal transduction may play a significant role in the progression of colorectal tumors in patients with familial adenomatous polyposis.