Induction of autophagy and inhibition of tumorigenesis by beclin 1
Abstract
The process of autophagy, or bulk degradation of cellular proteins through an autophagosomic-lysosomal pathway, is important in normal growth control and may be defective in tumour cells. However, little is known about the genetic mediators of autophagy in mammalian cells or their role in tumour development. The mammalian gene encoding Beclin 1, a novel Bcl-2-interacting, coiled-coil protein, has structural similarity to the yeast autophagy gene, apg6/vps30, and is mono-allelically deleted in 40-75% of sporadic human breast cancers and ovarian cancers. Here we show, using gene-transfer techniques, that beclin 1 promotes autophagy in autophagy-defective yeast with a targeted disruption of agp6/vps30, and in human MCF7 breast carcinoma cells. The autophagy-promoting activity of beclin 1 in MCF7 cells is associated with inhibition of MCF7 cellular proliferation, in vitro clonigenicity and tumorigenesis in nude mice. Furthermore, endogenous Beclin 1 protein expression is frequently low in human breast epithelial carcinoma cell lines and tissue, but is expressed ubiquitously at high levels in normal breast epithelia. Thus, beclin 1 is a mammalian autophagy gene that can inhibit tumorigenesis and is expressed at decreased levels in human breast carcinoma. These findings suggest that decreased expression of autophagy proteins may contribute to the development or progression of breast and other human malignancies.
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Binding of BCL2 to beclin inhibits the autophagy program.
“Furthermore, the binding of BCL2 to beclin seems to inhibit the autophagy program.”
From The common biology of cancer and ageing (2007) · cites this paper as [75]
Beclin 1 binds BCL2.
“The first link between autophagy and cancer came with the observation that the product of the mammalian gene beclin 1 ( Becn1 ), a homologue of the yeast autophagy gene VPS30 (also known as ATG6 ), bound to the human oncogene B-cell CLL/lymphoma 2 (BCL2) 75 .”
From The common biology of cancer and ageing (2007) · cites this paper as [75]
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- Authors
- Liang, X. H., Jackson, S., Seaman, M., Brown, K., Kempkes, B., Hibshoosh, H., & Levine, B.
- Affiliations
- Columbia University Irving Medical Center (US)
- Addenbrooke's Hospital (GB)
- Columbia University (US)
- Helmholtz Munich (DE)
- Corresponding author
- Levine, Beth
- Venue
- Nature
- Published
- 1999-12
- Volume
- 402
- Issue
- 6762
- Pages
- 672-676
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1784425676
- Cited by
- 3,347
- References
- 27
- Citations by year
- 2026: 41 · 2025: 106 · 2024: 115 · 2023: 114 · 2022: 146 · 2021: 148 · 2020: 192 · 2019: 163 · 2018: 156 · 2017: 189 · 2016: 200 · 2015: 199 · 2014: 200 · 2013: 237 · 2012: 185
- FWCI
- 16.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- Beclin-1, autophagy, carcinogenesis, breast cancer, ovarian cancer, MCF-7 cells, cell proliferation, clonogenicity, tumor suppression
- MeSH terms
- Beclin-1, Animals, Autophagy, Breast Neoplasms, Cell Transformation, Neoplastic, Chromosome Mapping, Chromosomes, Human, Pair 17, Fungal Proteins, Humans, Membrane Proteins, Mice, Nude, Neoplasm Transplantation, Proteins, Saccharomyces cerevisiae, Tumor Cells, Cultured, Gene Transfer Techniques, Saccharomyces cerevisiae Proteins, Vesicular Transport Proteins, Apoptosis Regulatory Proteins, Mice
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