Evidence map›Paper›PMID 22532567›Full record

ArticleThe Journal of biological chemistry2012

Androgen receptor splice variants activate androgen receptor target genes and support aberrant prostate cancer cell growth independent of canonical androgen receptor nuclear localization signal.

Siu Chiu Chan, Yingming Li, Scott M Dehm

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

Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
144citing papers in PubMed, 1 pooled it
19.8field-weighted citation impact, top 1% 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

144 citing papers in PubMed, 1 synthesis or guideline pooled it, 220 citations in OpenAlex.

  1. Pooled it
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  14. Stat5 induces androgen receptor (Science advances · 2024
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84 more citing papers are in PubMed but not listed here.

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

3 authors at 1 institution in 1 country.

Siu Chiu ChanMasonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Yingming Li
Scott M Dehm
University of Minnesota Medical Center · US

Funding

AR Transcriptional Activation Domains in Prostate Cancer ProgressionR21CA141011 · NCI · UNIVERSITY OF MINNESOTA · PI DEHM, SCOTT M. · 2009 to 2010
$365k
NCI NIH HHS CA141011NCI NIH HHS PC094384NCI NIH HHS R21 CA141011
6 · The paper itself

Abstract

Synthesis of truncated androgen receptor (AR) splice variants has emerged as an important mechanism of prostate cancer (PCa) resistance to AR-targeted therapy and progression to a lethal castration-resistant phenotype. However, the precise role of these factors at this stage of the disease is not clear due to loss of multiple COOH-terminal AR protein domains, including the canonical nuclear localization signal (NLS) in the AR hinge region. Despite loss of this NLS, we show that diverse truncated AR variant species have a basal level of nuclear localization sufficient for ligand-independent transcriptional activity. Whereas full-length AR requires Hsp90 and importin-β for active nuclear translocation, basal nuclear localization of truncated AR variants is independent of these classical signals. For a subset of truncated AR variants, this basal level of nuclear import can be augmented by unique COOH-terminal sequences that reconstitute classical AR NLS activity. However, this property is separable from ligand-independent transcriptional activity. Therefore, the AR splice variant core consisting of the AR NH(2)-terminal domain and DNA binding domain is sufficient for nuclear localization and androgen-independent transcriptional activation of endogenous AR target genes. Indeed, we show that truncated AR variants with nuclear as well as nuclear/cytoplasmic localization patterns can drive androgen-independent growth of PCa cells. Together, our data demonstrate that diverse truncated AR species with varying efficiencies of nuclear localization can contribute to castration-resistant PCa pathology by driving persistent ligand-independent AR transcriptional activity.

Indexed as

Alternative SplicingNuclear Localization SignalsActive Transport, Cell NucleusAnimalsbeta KaryopherinsCell NucleusChlorocebus aethiopsCOS CellsHSP90 Heat-Shock ProteinsHumansMaleNeoplasm ProteinsProstatic NeoplasmsReceptors, AndrogenTranscription, Geneticbeta KaryopherinsHSP90 Heat-Shock ProteinsNeoplasm ProteinsNuclear Localization SignalsReceptors, Androgen

Identifiers

PMID22532567
PMCPMC3366007
OpenAlexW2109537367

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.