Evidence map›Paper›PMID 21956655›Full record

ArticleThe Prostate2012

PSA regulates androgen receptor expression in prostate cancer cells.

Parmita Saxena, Marco Trerotola, Tao Wang, Jing Li, Aejaz Sayeed, Jennifer Vanoudenhove, Dave S Adams, Thomas J Fitzgerald, Dario C Altieri, Lucia R Languino

Abstract read
In one paragraph

Article in The Prostate, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

18 citing papers in PubMed, 39 citations in OpenAlex.

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  14. Quantitative Time-Resolved Fluorescence Imaging of Androgen Receptor and Prostate-Specific Antigen in Prostate Tissue Sections.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2016
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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

10 authors at 5 institutions in 1 country.

Parmita SaxenaDepartment of Cancer Biology, Prostate Cancer Discovery and Development Program, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Marco Trerotola
Tao Wang
Jing Li
Aejaz Sayeed
Jennifer Vanoudenhove
Dave S Adams
Thomas J Fitzgerald
Dario C Altieri
Lucia R Languino
University of Massachusetts Chan Medical School · USThomas Jefferson University · USSidney Kimmel Cancer Center · USThe Wistar Institute · USWorcester Polytechnic Institute · US

Funding

X-Ray Crystallography and Macromolecular CharacterizationP30CA056036 · NCI · THOMAS JEFFERSON UNIVERSITY · PI DANIEL P SILVER · 1995 to 2026
$94.8M
Role of Runx2 in prostate tumorigenesis and metastasisP01CA140043 · NCI · WISTAR INSTITUTE · PI ALTIERI, DARIO C · 2010 to 2021
$12.2M
CONTROL OF APOPTOSIS IN CANCER BY SURVIVINR01CA078810 · NCI · YALE UNIVERSITY · PI ALTIERI, DARIO C · 1998 to 2017
$5.5M
INTEGRIN SIGNALING PATHWAYS IN PROSTATE CANCERR01CA089720 · NCI · YALE UNIVERSITY · PI LANGUINO, LUCIA R. · 2001 to 2014
$2.8M
Beta1 Integrins and IGF-l Receptor in Prostate CancerR01CA109874 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LANGUINO, LUCIA R. · 2005 to 2015
$2.7M
NCI NIH HHS P01 CA140043NCI NIH HHS P01CA140043NCI NIH HHS P30 CA056036NCI NIH HHS P30 CA56036NCI NIH HHS R01 CA078810NCI NIH HHS R01 CA089720NCI NIH HHS R01CA089720NCI NIH HHS R01 CA109874NCI NIH HHS R01CA78810
6 · The paper itself

Abstract

backgroundProstate-specific antigen (PSA) is a pivotal downstream target gene of the androgen receptor (AR), and a serum biomarker to monitor prostate cancer (PrCa) progression. It has been reported that PSA transactivates AR, but the mechanistic requirements of this response have not been investigated.

methodsWe studied the localization of PSA, AR, and Src in intracellular compartments of synthetic androgen (R1881)-stimulated LNCaP and C4-2B PrCa cells, using immunofluorescence and subcellular fractionation approaches. We also investigated the effect of downregulation of PSA on AR expression by immunoblotting and real-time PCR using short hairpin RNA (shRNA) and small interfering RNA (siRNA). Src activity was analyzed by immunoblotting.

resultsR1881 stimulation induced nuclear localization of both PSA and AR in LNCaP and C4-2B PrCa cells as well as increased phosphorylation of Src. Stable shRNA or transient siRNA knockdown of PSA resulted in reduced AR protein levels as well as AR mRNA levels in C4-2B cells. Similar to C4-2B cells, ablation of AR levels upon silencing of PSA was also confirmed in VCaP cells, another androgen-independent cell line. Silencing of PSA did not cause significant changes in Src activation; besides, Src regulation by integrins did not appear to affect AR transcriptional activity.

conclusionsPSA localizes to nuclei of androgen-stimulated PrCa cells, and controls AR mRNA and protein levels. This regulatory loop is specific for PSA, does not involve known AR activators such as Src and AKT, and may contribute to AR signaling under conditions of increasing PSA levels in patients.

Indexed as

Cell Line, TumorDown-RegulationHumansMaleMetriboloneNeoplasms, Hormone-DependentPhosphorylationProstate-Specific AntigenProstatic NeoplasmsProto-Oncogene Proteins pp60(c-src)Receptors, AndrogenAR protein, humanMetriboloneProstate-Specific AntigenProto-Oncogene Proteins pp60(c-src)Receptors, Androgen

Identifiers

PMID21956655
PMCPMC3404455
OpenAlexW2017167084

What OpenQuestion holds

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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.