Abstract:
:Deregulation of Wnt signalling has recently been implicated in human renal cancer. Here, we directly test this association by using a Cre-LoxP strategy to inactivate the Adenomatous Polyposis Coli (Apc) gene in the murine renal epithelium. Mice homozygous for a conditional Apc allele were intercrossed with mice transgenic for Cre recombinase under control of the Cyp1A promoter, which delivers constitutive recombination within a proportion of cells in the renal epithelium. Inactivation of Apc leads to the accumulation of nuclear beta-catenin and the rapid development of multiple dysplastic foci. Renal carcinoma was observed with an earliest onset of 4 months. This predisposition was accelerated by p53 deficiency, reducing the earliest onset to 2 months. Compared to other murine models of kidney neoplasia, this represents particularly rapid onset of disease, and so implicates an important role for Apc in suppressing renal carcinoma.
journal_name
Oncogenejournal_title
Oncogeneauthors
Sansom OJ,Griffiths DF,Reed KR,Winton DJ,Clarke ARdoi
10.1038/sj.onc.1208956subject
Has Abstractpub_date
2005-12-08 00:00:00pages
8205-10issue
55eissn
0950-9232issn
1476-5594pii
1208956journal_volume
24pub_type
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