Evidence map›Paper›PMID 25263440›Full record

ArticleOncogene2015

TMPRSS2:ERG blocks neuroendocrine and luminal cell differentiation to maintain prostate cancer proliferation.

Z Mounir, F Lin, V G Lin, J M Korn, Y Yu, R Valdez, O H Aina, G Buchwalter, A B Jaffe, M Korpal and 6 more

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
5.6field-weighted citation impact, top 4% 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

44 citing papers in PubMed, 61 citations in OpenAlex.

  1. Article
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  16. Article
  17. Dynamics of Cellular Plasticity in Prostate Cancer Progression.Frontiers in molecular biosciences · 2020
    Review
  18. Review
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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

16 authors at 4 institutions in 1 country.

Z MounirNovartis Institutes for BioMedical Research, Cambridge, MA, USA.
F LinNovartis Institutes for BioMedical Research, Cambridge, MA, USA.
V G LinNovartis Institutes for BioMedical Research, Cambridge, MA, USA.
J M KornNovartis Institutes for BioMedical Research, Cambridge, MA, USA.
Y YuNovartis Institutes for BioMedical Research, Cambridge, MA, USA.
R ValdezNovartis Institutes for BioMedical Research, Cambridge, MA, USA.
O H AinaCenter for Comparative Medicine, University of California, Davis, CA, USA.
G Buchwalter1] Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA [2] Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.
A B JaffeNovartis Institutes for BioMedical Research, Cambridge, MA, USA.
M KorpalNovartis Institutes for BioMedical Research, Cambridge, MA, USA.
P ZhuNovartis Institutes for BioMedical Research, Cambridge, MA, USA.
M Brown1] Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA [2] Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.
R D CardiffCenter for Comparative Medicine, University of California, Davis, CA, USA.
J L RocnikNovartis Institutes for BioMedical Research, Cambridge, MA, USA.
Y YangNovartis Institutes for BioMedical Research, Cambridge, MA, USA.
R PagliariniNovartis Institutes for BioMedical Research, Cambridge, MA, USA.
Novartis (United States) · USUniversity of California, Davis · USDana-Farber Cancer Institute · USHarvard University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The biological outcome of TMPRSS2:ERG chromosomal translocations in prostate cancer (PC) remains poorly understood. To address this, we compared the transcriptional effects of TMPRSS2:ERG expression in a transgenic mouse model with those of ERG knockdown in a TMPRSS2:ERG-positive PC cell line. This reveals that ERG represses the expression of a previously unreported set of androgen receptor (AR)-independent neuronal genes that are indicative of neuroendocrine (NE) cell differentiation-in addition to previously reported AR-regulated luminal genes. Cell sorting and proliferation assays performed after sustained ERG knockdown indicate that ERG drives proliferation and blocks the differentiation of prostate cells to both NE and luminal cell types. Inhibition of ERG expression in TMPRSS2:ERG-positive PC cells through blockade of AR signaling is tracked with increased NE gene expression. We also provide evidence that these NE cells are resistant to pharmacological AR inhibition and can revert to the phenotype of parental cells upon restoration of AR/ERG signaling. Our findings highlight an ERG-regulated mechanism capable of repopulating the parent tumor through the transient generation of an anti-androgen therapy-resistant cell population, suggesting that ERG may have a direct role in preventing resistance to anti-androgen therapy.

Indexed as

AnimalsAntibiotics, AntineoplasticBenzamidesCell DifferentiationCell Line, TumorCell ProliferationDisease Models, AnimalDoxorubicinEpithelial CellsGene Expression ProfilingGene Expression Regulation, NeoplasticHumansImmunohistochemistryMaleMice, TransgenicMicroscopy, ConfocalAntibiotics, AntineoplasticBenzamidesDoxorubicinenzalutamideERG protein, humanNitrilesOncogene Proteins, FusionPhenylthiohydantoinReceptors, AndrogenSerine EndopeptidasesTMPRSS2 protein, humanTrans-ActivatorsTranscriptional Regulator ERG

Identifiers

PMID25263440
OpenAlexW1965383997

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.