The DOI matches its Crossref record; 71 of the 71 references it cites were found in a registry or an index.
Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene
Open accessAbstract
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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“In this case, the haploinsufficient mice developed tumours, indicating that autophagy might act as an important in vivo tumour suppressor 76, 77 .”
From The common biology of cancer and ageing (2007) · cites this paper as [77]
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Metadata
- Authors
- Qu, X., Yu, J., Bhagat, G., Furuya, N., Hibshoosh, H., Troxel, A., Rosen, J., Eskelinen, E.-L., Mizushima, N., Ohsumi, Y., Cattoretti, G., & Levine, B.
- Affiliations
- Columbia University (US)
- Baylor College of Medicine (US)
- National Institute for Basic Biology (JP)
- Corresponding author
- Levine, Beth
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2003-12-15
- Volume
- 112
- Issue
- 12
- Pages
- 1809-1820
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC297002
- OpenAlex
- W2115886998
- Cited by
- 2,311
- References
- 71
- Citations by year
- 2026: 46 · 2025: 55 · 2024: 75 · 2023: 85 · 2022: 110 · 2021: 142 · 2020: 122 · 2019: 125 · 2018: 123 · 2017: 122 · 2016: 125 · 2015: 144 · 2014: 154 · 2013: 179 · 2012: 130
- FWCI
- 21.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Tokyo Tech Research Repository (Tokyo Institute of Technology) (submittedVersion)
- Funders
- National Institutes of Health (5r01ai044157-03, CA16303)
- National Cancer Institute (R01 CA84254, R01CA016303, R01 CA16303, R01CA084254)
- National Institute of Allergy and Infectious Diseases (R01 AI44157)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- Beclin-1, autophagy, tumor suppression, haploinsufficiency, hepatitis B virus, precancerous lesions, cell proliferation, monoallelic deletion, carcinogenesis
- MeSH terms
- Beclin-1, Alleles, Animals, Autophagy, Cell Division, Cell Transformation, Neoplastic, Female, Genotype, Hepatitis B virus, Heterozygote, Male, Membrane Proteins, Mice, Inbred C57BL, Mice, Mutant Strains, Mice, Transgenic, Microscopy, Fluorescence, Models, Genetic, Mutation, Neoplasms, Proteins, Recombination, Genetic, Thymus Gland, Time Factors, Blotting, Southern, DNA Primers, Mice, Knockout, Cell Line, Tumor, Apoptosis Regulatory Proteins, Mice
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