Induction of autophagy and inhibition of tumorigenesis by beclin 1

Xiao Huan Liang, Saadiya Jackson, Matthew Seaman, Kristy Brown, Bettina Kempkes, Hanina Hibshoosh, Beth Levine

Research output: Contribution to journalArticle

2216 Citations (Scopus)

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 (ref. 3), a novel Bcl-2- interacting, coiled-coil protein, has structural similarity to the yeast autophagy gene, apg6/vps30 (refs 4, 5), 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.

Original languageEnglish (US)
Pages (from-to)672-676
Number of pages5
JournalNature
Volume402
Issue number6762
DOIs
StatePublished - Dec 9 1999

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Autophagy
Carcinogenesis
Breast Neoplasms
Breast
Yeasts
Genes
Gene Transfer Techniques
Neoplasms
Beclin-1
MCF-7 Cells
Nude Mice
Ovarian Neoplasms
Proteolysis
Proteins
Epithelium
Epithelial Cells
Cell Proliferation
Cell Line
Growth

ASJC Scopus subject areas

  • General

Cite this

Liang, X. H., Jackson, S., Seaman, M., Brown, K., Kempkes, B., Hibshoosh, H., & Levine, B. (1999). Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature, 402(6762), 672-676. https://doi.org/10.1038/45257

Induction of autophagy and inhibition of tumorigenesis by beclin 1. / Liang, Xiao Huan; Jackson, Saadiya; Seaman, Matthew; Brown, Kristy; Kempkes, Bettina; Hibshoosh, Hanina; Levine, Beth.

In: Nature, Vol. 402, No. 6762, 09.12.1999, p. 672-676.

Research output: Contribution to journalArticle

Liang, XH, Jackson, S, Seaman, M, Brown, K, Kempkes, B, Hibshoosh, H & Levine, B 1999, 'Induction of autophagy and inhibition of tumorigenesis by beclin 1', Nature, vol. 402, no. 6762, pp. 672-676. https://doi.org/10.1038/45257
Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature. 1999 Dec 9;402(6762):672-676. https://doi.org/10.1038/45257
Liang, Xiao Huan ; Jackson, Saadiya ; Seaman, Matthew ; Brown, Kristy ; Kempkes, Bettina ; Hibshoosh, Hanina ; Levine, Beth. / Induction of autophagy and inhibition of tumorigenesis by beclin 1. In: Nature. 1999 ; Vol. 402, No. 6762. pp. 672-676.
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