Low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA levels are coordinately reduced in human renal cell carcinoma

The current investigation aimed to determine if the gene expression of important structures in cholesterol metabolism is altered in a solid human tumor. For this purpose we determined low density lipoprotein (LDL) receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) transcript levels and total tissue cholesterol in both tumors and normal kidney tissue in a series of samples from 29 patients with renal cell carcinoma, (RCC). LDL-receptor- and HMG-CoA reductase mRNA levels were reduced in tumor tissue as compared with normal kidney tissue (by 29%, P < 0.03, and 31%, P < 0.001 respectively). The LDL-receptor mRNA levels correlated significantly to the mRNA levels for HMG-CoA reductase in tumors (P < 0.0001) and normal kidney tissue (P < 0.03). The total tissue cholesterol levels in tumors were 5-fold elevated (P < 0.0001) as compared to normal kidney. We conclude that the mRNA levels for LDL-receptor and HMG-CoA reductase are regulated in parallel in human RCC and in normal kidney, and that these mRNA are generally reduced in human RCC. The data indicate that the accumulation of cholesterol in RCC may not be due to increased LDL receptor expression or de novo synthesis of cholesterol.