Cholesterol and the development of clear-cell renal carcinoma

The majority of kidney cancers are clear-cell carcinomas (ccRCC), characterized by the accumulation of cholesterol, cholesterol esters, other neutral lipids and glycogen. Rather than being a passive bystander, the clear-cell phenotype is suggested to be a biomarker of deregulated cholesterol and lipid biosynthesis, which plays an important role in development of the disease. One clue to this relationship has come from the elucidation of the hereditary kidney cancer gene, TRC8, which functions partly to degrade key regulators of endogenous cholesterol and lipid biosynthesis. In addition, deregulation of the mevalonate pathway has been shown to play a key role in cellular transformation and invasion. These findings are supported by considerable epidemiologic data linking obesity and the deregulation of lipid biosynthesis to ccRCC.