1. ¹Department of Medical Oncology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, The Netherlands
2. ²Department of Pulmonary Diseases, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, The Netherlands

Correspondence: Dr RH Giles, Laboratory of Experimental Oncology, Department of Medical Oncology, University Medical Center Utrecht, Heidelberglaan 100, Room F02.126, Utrecht 3584 CX, The Netherlands. Tel: +31-30-253-9729; Fax: +31-30-253-8479; E-mail: r.giles@umcutrecht.nl

³These authors contributed equally.

⁴Current address: 2nd Division of Pediatrics, G. Gaslini Institute for Children, University of Genoa, Italy.

Received 30 May 2007; Revised 22 August 2007; Accepted 28 August 2007; Published online 3 October 2007.

Abstract

Patients with von Hippel–Lindau (VHL) disease often develop VHL-/- kidney cysts, which possibly progress into clear-cell renal carcinomas (ccRCCs). Recent data link the VHL gene product to formation of the primary cilium, an organelle that extends apically into the renal lumen. Exactly how VHL induces ciliogenesis or function is unknown. Here, we demonstrate that ciliary assembly and mechanotransduction is rapidly restored in VHL-/- ccRCC cells upon ectopic reconstitution of wild-type – but not variant alleles of – VHL. These data support and expand recent studies implicating a role for VHL in the initiation of ciliogenesis. Furthermore, reduction of cellular levels of VHL in this cell system was associated with fewer ciliated cells, suggesting a role for VHL in ciliary maintenance.