Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene.

http://www.ncbi.nlm.nih.gov/pubmed/14638851

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.

Pubmed ID: 14638851 RIS Download

Mesh terms: Alleles | Animals | Apoptosis Regulatory Proteins | Autophagy | Blotting, Southern | Cell Division | Cell Line, Tumor | Cell Transformation, Neoplastic | DNA Primers | Female | Genotype | Hepatitis B virus | Heterozygote | Male | Membrane Proteins | Mice | Mice, Inbred C57BL | Mice, Knockout | Mice, Mutant Strains | Mice, Transgenic | Microscopy, Fluorescence | Models, Genetic | Mutation | Neoplasms | Proteins | Recombination, Genetic | Thymus Gland | Time Factors

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NIAID NIH HHS, Id: R01 AI44157
  • Agency: NCI NIH HHS, Id: R01 CA16303
  • Agency: NCI NIH HHS, Id: R01 CA84254

Mouse Genome Informatics (Data, Gene Annotation)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.