3-Hydroxy-3-methylglutaryl coenzyme A reductase activity and low-density lipoprotein receptor expression in diffuse-type and intestinal-type human gastric cancer.

Abstract

Cancer cells require more cholesterol than normal cells. This requirement may be satisfied by higher hydroxymethylglutaryl coenzyme A reductase activity or low-density lipoprotein receptor expression or both. We investigated hydroxymethylglutaryl coenzyme A reductase activity and low-density lipoprotein receptor expression in samples of gastric carcinoma and normal mucosa obtained from 30 patients. The samples of gastric carcinoma were divided into two categories according to Lauren's classification: diffuse-type and intestinal-type. Hydroxymethylglutaryl coenzyme A reductase activity was measured by radiometric assay and low-density lipoprotein receptor expression was measured by enzyme-linked immunosorbent assay. Hydroxy-methyl-glutaryl-coenzyme A reductase activity was significantly higher in neoplastic tissue than in normal mucosa, both in diffuse-type and intestinal-type gastric cancer. Low-density lipoprotein receptor levels were significantly lower in neoplastic tissue than in normal mucosa of diffuse-type gastric cancer, whereas no significant difference was present between neoplastic tissue and normal mucosa in intestinal-type gastric cancer. Hydroxymethylglutaryl coenzyme A reductase activity did not differ between intestinal-type and diffuse-type neoplastic samples, while low-density lipoprotein receptor levels were significantly higher in intestinal-type than in diffuse-type gastric cancer tissue. These findings show different behavior of cholesterol metabolism in the two types of gastric carcinoma and, therefore, suggest that different therapeutic strategies should be adopted.