Formation of primary cilia in the renal epithelium is regulated by the von hippel-lindau tumor suppressor protein

• Published in: Journal of the American Society of Nephrology Vol. 17; no. 7; pp. 1801 - 1806
• Main Authors: ESTEBAN, Miguel A, HARTEN, Sarah K, TRAN, Maxine G, MAXWELL, Patrick H
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.07.2006
• Subjects: Biological and medical sciences; Carcinoma, Renal Cell - physiopathology; Cell Line; Cilia - physiology; Cysts - pathology; Epithelium - pathology; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Kidney - pathology; Kidneys; Medical sciences; Nephrology. Urinary tract diseases; Neurology; Tubulin - analysis; Tumor Cells, Cultured; Tumors of the nervous system. Phacomatoses; Tumors of the urinary system; von Hippel-Lindau Disease - pathology; Von Hippel-Lindau Tumor Suppressor Protein - genetics; Von Hippel-Lindau Tumor Suppressor Protein - metabolism; Kidney disease; Human; Nervous system diseases; Nephrology; Urinary system disease; Phacomatosis; Pathogenesis; Kidney cyst; Cardiovascular disease; Epithelium; Kidney; Urology; Genetic disease; Vascular disease; Eye disease; Central nervous system disease; Genetics; Benign neoplasm; Von Hippel Lindau disease; Cilia; Tumor suppressor gene
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/asn.2006020181

Growing evidence points to defects in the primary cilium as a critical mechanism underlying renal cyst development. Inactivation of the VHL gene is responsible for the autosomal dominant condition von Hippel-Lindau (VHL) disease and is implicated in most sporadic clear cell renal carcinomas. Manifestations of VHL disease include cysts in several organs, particularly in the kidney. Here it is shown that VHL inactivation is associated with abrogation of the primary cilium in renal cysts of patients with VHL disease and in VHL-defective cell lines. Complementation of VHL-defective clear cell renal carcinoma cell lines with wild-type VHL restored primary cilia. Moreover, it is shown that the effects of VHL on the primary cilium are mediated substantially via hypoxia-inducible factor. The effect of VHL status on the primary cilium provides a potential mechanism for renal cyst development in VHL disease and may help in the understanding of how VHL acts as a tumor suppressor.