Abnormal cholesterol metabolism in a malignant Ras-mutated rat fibroblast line

Autor: Bianca Fuhrman, Efrat Wolfovitz, Irit Maor, J.Gerald Brook
Rok vydání: 1997
Předmět:
Zdroj: Pathophysiology. 4:235-240
ISSN: 0928-4680
DOI: 10.1016/s0928-4680(97)00025-4
Popis: Some cancer patients demonstrate low levels of plasma cholesterol. This has been explained as resulting from a defect in the cholesterol feedback control in tumor cells. The objective of this study was to determine the presence of a relationship between cholesterol metabolism and regulation, and between the occurrence of mutated Ras protein activity. Total cholesterol mass in Ras-mutated rat embryo fibroblasts was 2 times less than that in control cells (non-mutated fibroblasts). Low-density lipoprotein (LDL) uptake, as determined by 125 I-labeled LDL degradation was 2-fold higher in the Ras-mutated cells. Downregulation of LDL uptake in both mutated and non-mutated cells was similar. Cholesterol synthesis in the mutated cells was lower by 50–66%, compared with non-mutated cells. There was no change in cholesterol efflux between the two cell lines. Thus, it appears that in these mutated cells, overutilization of the farnesyl pathway results in decreased accumulation of cholesterol in the cells. We suggest that a relationship between mutated Ras protein activity and cholesterol metabolism is present.
Databáze: OpenAIRE