Formation of primary cilia in the renal epithelium is regulated by the von Hippel-Lindau tumor suppressor protein.
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.
Esteban
Miguel A
MA
Renal Laboratory, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
Harten
Sarah K
SK
Tran
Maxine G
MG
Maxwell
Patrick H
PH
D002292:Carcinoma, Renal Cell / Q000503:physiopathology*; D002460:Cell Line; D002923:Cilia / Q000502:physiology*; D003560:Cysts / Q000473:pathology; D004848:Epithelium / Q000473:pathology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry; D007668:Kidney / Q000473:pathology*; D014404:Tubulin / Q000032:analysis; D014407:Tumor Cells, Cultured; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics / Q000378:metabolism*; D006623:von Hippel-Lindau Disease / Q000473:pathology
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014404:Tubulin; D051794:Von Hippel-Lindau Tumor Suppressor Protein