PMID- 10604474
OWN - NLM
STAT- MEDLINE
DCOM- 20000104
LR  - 20161124
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 402
IP  - 6762
DP  - 1999 Dec 9
TI  - Induction of autophagy and inhibition of tumorigenesis by beclin 1.
PG  - 672-6
AB  - 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.
FAU - Liang, X H
AU  - Liang XH
AD  - Department of Medicine, Columbia University College of Physicians & Surgeons, New
      York, New York 10032, USA.
FAU - Jackson, S
AU  - Jackson S
FAU - Seaman, M
AU  - Seaman M
FAU - Brown, K
AU  - Brown K
FAU - Kempkes, B
AU  - Kempkes B
FAU - Hibshoosh, H
AU  - Hibshoosh H
FAU - Levine, B
AU  - Levine B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (BECN1 protein, human)
RN  - 0 (Beclin-1)
RN  - 0 (Becn1 protein, mouse)
RN  - 0 (Fungal Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Proteins)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 0 (VPS30 protein, S cerevisiae)
RN  - 0 (Vesicular Transport Proteins)
SB  - IM
MH  - Animals
MH  - Apoptosis Regulatory Proteins
MH  - *Autophagy/genetics
MH  - Beclin-1
MH  - Breast Neoplasms/genetics/metabolism
MH  - *Cell Transformation, Neoplastic
MH  - Chromosome Mapping
MH  - Chromosomes, Human, Pair 17
MH  - Fungal Proteins/genetics
MH  - Gene Transfer Techniques
MH  - Humans
MH  - Membrane Proteins
MH  - Mice
MH  - Mice, Nude
MH  - Neoplasm Transplantation
MH  - Proteins/genetics/metabolism/*physiology
MH  - Saccharomyces cerevisiae/genetics
MH  - *Saccharomyces cerevisiae Proteins
MH  - Tumor Cells, Cultured
MH  - Vesicular Transport Proteins
EDAT- 1999/12/22 09:00
MHDA- 2001/03/23 10:01
CRDT- 1999/12/22 09:00
PHST- 1999/12/22 09:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/12/22 09:00 [entrez]
AID - 10.1038/45257 [doi]
PST - ppublish
SO  - Nature. 1999 Dec 9;402(6762):672-6. doi: 10.1038/45257.