Levels of the Autophagy-Related 5 Protein Affect Progression and Metastasis of Pancreatic Tumors in Mice.
Animals
Autophagy
Autophagy-Related Protein 5
/ deficiency
Carcinoma, Pancreatic Ductal
/ genetics
Cathepsins
/ genetics
Cell Movement
Cell Proliferation
Cell Transformation, Neoplastic
/ genetics
Disease Progression
Gene Expression Regulation, Neoplastic
Genes, ras
Heterozygote
Homozygote
Mice, Knockout
Pancreatic Neoplasms
/ genetics
Signal Transduction
Tumor Burden
Tumor Cells, Cultured
Atg5 Levels
Ca(2+)
Cathepsins
Mitochondria
Pancreatic Carcinogenesis
Journal
Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
23
12
2017
revised:
27
09
2018
accepted:
28
09
2018
pubmed:
9
10
2018
medline:
29
1
2019
entrez:
9
10
2018
Statut:
ppublish
Résumé
Cells in pancreatic ductal adenocarcinoma (PDAC) undergo autophagy, but its effects vary with tumor stage and genetic factors. We investigated the consequences of varying levels of the autophagy related 5 (Atg5) protein on pancreatic tumor formation and progression. We generated mice that express oncogenic Kras in primary pancreatic cancer cells and have homozygous disruption of Atg5 (A5;Kras) or heterozygous disruption of Atg5 (A5 A5 In mice that express oncogenic Kras in pancreatic cells, heterozygous disruption of Atg5 and reduced protein levels promotes tumor development, whereas homozygous disruption of Atg5 blocks tumorigenesis. Therapeutic strategies to alter autophagy in PDAC should consider the effects of ATG5 levels to avoid the expansion of resistant and highly aggressive cells.
Sections du résumé
BACKGROUND AND AIMS
Cells in pancreatic ductal adenocarcinoma (PDAC) undergo autophagy, but its effects vary with tumor stage and genetic factors. We investigated the consequences of varying levels of the autophagy related 5 (Atg5) protein on pancreatic tumor formation and progression.
METHODS
We generated mice that express oncogenic Kras in primary pancreatic cancer cells and have homozygous disruption of Atg5 (A5;Kras) or heterozygous disruption of Atg5 (A5
RESULTS
A5
CONCLUSIONS
In mice that express oncogenic Kras in pancreatic cells, heterozygous disruption of Atg5 and reduced protein levels promotes tumor development, whereas homozygous disruption of Atg5 blocks tumorigenesis. Therapeutic strategies to alter autophagy in PDAC should consider the effects of ATG5 levels to avoid the expansion of resistant and highly aggressive cells.
Identifiants
pubmed: 30296435
pii: S0016-5085(18)35087-X
doi: 10.1053/j.gastro.2018.09.053
pii:
doi:
Substances chimiques
Atg5 protein, mouse
0
Autophagy-Related Protein 5
0
Cathepsins
EC 3.4.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
203-217.e20Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.