Evidence map›Paper›PMID 25012505›Full record

ArticleCell death and differentiation2014

Loss of Prkar1a leads to Bcl-2 family protein induction and cachexia in mice.

L Gangoda, M Doerflinger, R Srivastava, N Narayan, L E Edgington, J Orian, C Hawkins, L A O'Reilly, H Gu, M Bogyo and 3 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death and differentiation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.0field-weighted citation impact, top 21% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 15 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 2 countries.

L GangodaDepartment of Biochemistry, La Trobe Institute of Molecular Science, La Trobe University, Melbourne, Victoria, Australia.
M DoerflingerDepartment of Biochemistry, La Trobe Institute of Molecular Science, La Trobe University, Melbourne, Victoria, Australia.
R SrivastavaDepartment of Biochemistry, La Trobe Institute of Molecular Science, La Trobe University, Melbourne, Victoria, Australia.
N NarayanThe Walter and Eliza Hall Institute, Melbourne, Victoria, Australia.
L E EdgingtonDepartment of Biochemistry, La Trobe Institute of Molecular Science, La Trobe University, Melbourne, Victoria, Australia.
J OrianDepartment of Biochemistry, La Trobe Institute of Molecular Science, La Trobe University, Melbourne, Victoria, Australia.
C HawkinsDepartment of Biochemistry, La Trobe Institute of Molecular Science, La Trobe University, Melbourne, Victoria, Australia.
L A O'Reilly1] The Walter and Eliza Hall Institute, Melbourne, Victoria, Australia [2] Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia.
H GuInstitut de Recherches Cliniques de Montréal (IRCM) Department of Microbiology and Immunology, University of Montreal and Division of Experimental Medicine, McGill University Montreal, Montreal, Quebec, Canada.
M BogyoCancer Biology Program, Department of Pathology, Stanford School of Medicine, Stanford, CA, USA.
P EkertThe Walter and Eliza Hall Institute, Melbourne, Victoria, Australia.
A Strasser1] The Walter and Eliza Hall Institute, Melbourne, Victoria, Australia [2] Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia.
H PuthalakathDepartment of Biochemistry, La Trobe Institute of Molecular Science, La Trobe University, Melbourne, Victoria, Australia.
La Trobe University · AUWalter and Eliza Hall Institute of Medical Research · AUStanford Medicine · US

Funding

Leveraging innovative technologies in basic and clinical cancer researchT32CA009302 · NCI · STANFORD UNIVERSITY · PI LAURA D ATTARDI, Aaron M Newman · 1985 to 2026
$19.1M
NCI NIH HHS T32 CA009302
6 · The paper itself

Abstract

Loss of function mutations in the Prkar1a gene are the cause of most cases of Carney complex disorder. Defects in Prkar1a are thought to cause hyper-activation of PKA signalling, which drives neoplastic transformation, and Prkar1a is therefore considered to be a tumour suppressor. Here we show that loss of Prkar1a in genetically modified mice caused transcriptional activation of several proapoptotic Bcl-2 family members and thereby caused cell death. Interestingly, combined loss of Bim and Prkar1a increased colony formation of fibroblasts in culture and promoted their growth as tumours in immune-deficient mice. Apart from inducing apoptosis, systemic deletion of Prkar1a caused cachexia with muscle loss, macrophage activation and increased lipolysis as well as serum triglyceride levels. Loss of single allele of Prkar1a did not enhance tumour development in a skin cancer model, but surprisingly, when combined with the loss of Bim, caused a significant delay in tumorigenesis and this was associated with upregulation of other BH3-only proteins, PUMA and NOXA. These results show that loss of Prkar1a can only promote tumorigenesis when Prkar1a-mediated apoptosis is somehow countered.

Indexed as

AnimalsApoptosisApoptosis Regulatory ProteinsCachexiaCarcinogenesisCell Transformation, NeoplasticCyclic AMP-Dependent Protein Kinase RIalpha SubunitFibroblastsGene DeletionGenes, Tumor SuppressorMiceProto-Oncogene Proteins c-bcl-2Apoptosis Regulatory ProteinsCyclic AMP-Dependent Protein Kinase RIalpha SubunitPrkar1a protein, mouseProto-Oncogene Proteins c-bcl-2

Identifiers

PMID25012505
PMCPMC4211378
OpenAlexW2131175026

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.