References
Query Results -- Details
MGI Accession ID: MGI:2682498
J Number: J:86953
Other Accession IDs:
Title: Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene.
Authors: Qu X; Yu J; Bhagat G; Furuya N; Hibshoosh H; Troxel A; Rosen J; Eskelinen EL; Mizushima N; Ohsumi Y; Cattoretti G; Levine B
Journal: J Clin Invest
Volume: 112
Issue: 12
Date: 2003 Dec
Year: 2003
Pages: 1809-20
Review Status: Peer Reviewed
Abstract:
Malignant cells often display defects in autophagy, an evolutionarily conserved pathway for degrading long-lived proteins and cytoplasmic organelles. However, as yet, there is no genetic evidence for a role of autophagy genes in tumor suppression. The beclin 1 autophagy gene is monoallelically deleted in 40-75% of cases of human sporadic breast, ovarian, and prostate cancer. Therefore, we used a targeted mutant mouse model to test the hypothesis that monoallelic deletion of beclin 1 promotes tumorigenesis. Here we show that heterozygous disruption of beclin 1 increases the frequency of spontaneous malignancies and accelerates the development of hepatitis B virus-induced premalignant lesions. Molecular analyses of tumors in beclin 1 heterozygous mice show that the remaining wild-type allele is neither mutated nor silenced. Furthermore, beclin 1 heterozygous disruption results in increased cellular proliferation and reduced autophagy in vivo. These findings demonstrate that beclin 1 is a haplo-insufficient tumor-suppressor gene and provide genetic evidence that autophagy is a novel mechanism of cell-growth control and tumor suppression. Thus, mutation of beclin 1 or other autophagy genes may contribute to the pathogenesis of human cancers.
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