References
Query Results -- Details
MGI Accession ID: MGI:3797711
J Number: J:137073
Other Accession IDs:
Title: pVHL and PTEN tumour suppressor proteins cooperatively suppress kidney cyst formation.
Authors: Frew IJ; Thoma CR; Georgiev S; Minola A; Hitz M; Montani M; Moch H; Krek W
Journal: EMBO J
Volume: 27
Issue: 12
Date: 2008 Jun 18
Year: 2008
Pages: 1747-57
Review Status: Peer Reviewed
Abstract:
In patients with von Hippel-Lindau (VHL) disease, renal cysts and clear cell renal cell carcinoma (ccRCC) arise from renal tubular epithelial cells containing biallelic inactivation of the VHL tumour suppressor gene. However, it is presumed that formation of renal cysts and their conversion to ccRCC involve additional genetic changes at other loci. Here, we show that cystic lesions in the kidneys of patients with VHL disease also demonstrate activation of the phosphatidylinositol-3-kinase (PI3K) pathway. Strikingly, combined conditional inactivation of Vhlh and the Pten tumour suppressor gene, which normally antagonises PI3K signalling, in the mouse kidney, elicits cyst formation after short latency, whereas inactivation of either tumour suppressor gene alone failed to produce such a phenotype. Interestingly, cells lining these cysts frequently lack a primary cilium, a microtubule-based cellular antenna important for suppression of uncontrolled kidney epithelial cell proliferation and cyst formation. Our results support a model in which the PTEN tumour suppressor protein cooperates with pVHL to suppress cyst development in the kidney.
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