Effects of iron deficiency in a Von Hippel-Lindau disease cellular model system

Effects of iron deficiency in a Von Hippel-Lindau disease cellular model system

Vol. 1, no. 1, 31-42
Author:
Hannah Teeuw
University College Utrecht, Utrecht University

Abstract

Von Hippel-Lindau disease (VHL) is characterized by mutations in the VHL gene, which encodes a protein (pVHL) that is involved in cellular oxygen homeostasis. When pVHL fails to recognize and degrade the hypoxia-inducible factor (HIF) transcription factor under normoxic conditions, inappropriate expression of HIF target genes facilitates tumorigenesis in the kidneys, retina, cerebellar blood vessels, and other organs. Importantly, pVHL-HIF binding requires hydroxylation of HIF, and this reaction depends on iron as a cofactor. It was therefore hypothesized that iron deficiency can affect the course of VHL. Low ferritin levels are in fact observed in some VHL patients, but the clinical relevance of this iron deficiency is unclear. This investigation focused on the impact of iron deficiency on growth and HIF target gene expression of 786-0 pVHL-deficient renal cell carcinoma (RCC) cells. Iron deficiency decreased growth and increased the expression of HIF target genes, indicating a potentially tumorigenic effect on RCC cells.

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