Evidence map›Paper›PMID 20823238›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2010

Constitutively active androgen receptor splice variants expressed in castration-resistant prostate cancer require full-length androgen receptor.

Philip A Watson, Yinan F Chen, Minna D Balbas, John Wongvipat, Nicholas D Socci, Agnes Viale, Kwanghee Kim, Charles L Sawyers

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

Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 381 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
381citing papers in PubMed, 2 pooled it
42.1field-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

381 citing papers in PubMed, 2 syntheses or guidelines pooled it, 635 citations in OpenAlex.

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  4. TBCRC 032 IB/II Multicenter Study: Molecular Insights to AR Antagonist and PI3K Inhibitor Efficacy in Patients with ARClinical cancer research : an official journal of the American Association for Cancer Research · 2020
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321 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Philip A WatsonHuman Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Yinan F Chen
Minna D Balbas
John Wongvipat
Nicholas D Socci
Agnes Viale
Kwanghee Kim
Charles L Sawyers
Memorial Sloan Kettering Cancer Center · USHoward Hughes Medical Institute · USUniversity of California, Los Angeles · US

Funding

Howard Hughes Medical Institute
6 · The paper itself

Abstract

Androgen receptor (AR) splice variants lacking the ligand binding domain (ARVs), originally isolated from prostate cancer cell lines derived from a single patient, are detected in normal and malignant human prostate tissue, with the highest levels observed in late stage, castration-resistant prostate cancer. The most studied variant (called AR-V7 or AR3) activates AR reporter genes in the absence of ligand and therefore, could play a role in castration resistance. To explore the range of potential ARVs, we screened additional human and murine prostate cancer models using conventional and next generation sequencing technologies and detected several structurally diverse AR isoforms. Some, like AR-V7/AR3, display gain of function, whereas others have dominant interfering activity. We also find that ARV expression increases acutely in response to androgen withdrawal, is suppressed by testosterone, and in some models, is coupled to full-length AR (AR-FL) mRNA production. As expected, constitutively active, ligand-independent ARVs such as AR-V7/AR3 are sufficient to confer anchorage-independent (in vitro) and castration-resistant (in vivo) growth. Surprisingly, this growth is blocked by ligand binding domain-targeted antiandrogens, such as MDV3100, or by selective siRNA silencing of AR-FL, indicating that the growth-promoting effects of ARVs are mediated through AR-FL. These data indicate that the increase in ARV expression in castrate-resistant prostate cancer is an acute response to castration rather than clonal expansion of castration or antiandrogen-resistant cells expressing gain of function ARVs, and furthermore, they provide a strategy to overcome ARV function in the clinic.

Indexed as

Alternative SplicingGene Expression Regulation, NeoplasticAmino Acid SequenceAndrogen Receptor AntagonistsAndrogensAnimalsCastrationCell Line, TumorDisease Models, AnimalExonsHumansMaleMiceMolecular Sequence DataProstatic NeoplasmsProtein Structure, TertiaryAndrogen Receptor AntagonistsAndrogensReceptors, AndrogenRNA, Messenger

Identifiers

PMID20823238
PMCPMC2947883
OpenAlexW2083926838

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.