Evidence map›Paper›PMID 24975515›Full record

ArticleScientific reports2014

HE4 expression is associated with hormonal elements and mediated by importin-dependent nuclear translocation.

Elizabeth Lokich, Rakesh K Singh, Alex Han, Nicole Romano, Naohiro Yano, Kyukwang Kim, Richard G Moore

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

Article in Scientific reports, 2014. 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
1.4field-weighted citation impact, top 19% 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, 50 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Iranian journal of pathology · 2021
    Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Distinct terminal and cell body mechanisms in the nociceptor mediate hyperalgesic priming.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015
    Article
  17. Expression and diagnostic value of HE4 in pancreatic adenocarcinoma.International journal of molecular sciences · 2015
    Article
  18. Article
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

7 authors at 1 institution in 1 country.

Elizabeth Lokich1] Program in Women's Oncology, Department of Obstetrics and Gynecology, Women and Infants' Hospital, Alpert Medical School at Brown University, Providence, RI, 02905, USA [2].
Rakesh K SinghProgram in Women's Oncology, Department of Obstetrics and Gynecology, Women and Infants' Hospital, Alpert Medical School at Brown University, Providence, RI, 02905, USA.
Alex Han1] Program in Women's Oncology, Department of Obstetrics and Gynecology, Women and Infants' Hospital, Alpert Medical School at Brown University, Providence, RI, 02905, USA [2].
Nicole RomanoProgram in Women's Oncology, Department of Obstetrics and Gynecology, Women and Infants' Hospital, Alpert Medical School at Brown University, Providence, RI, 02905, USA.
Naohiro YanoProgram in Women's Oncology, Department of Obstetrics and Gynecology, Women and Infants' Hospital, Alpert Medical School at Brown University, Providence, RI, 02905, USA.
Kyukwang KimProgram in Women's Oncology, Department of Obstetrics and Gynecology, Women and Infants' Hospital, Alpert Medical School at Brown University, Providence, RI, 02905, USA.
Richard G MooreProgram in Women's Oncology, Department of Obstetrics and Gynecology, Women and Infants' Hospital, Alpert Medical School at Brown University, Providence, RI, 02905, USA.
Brown University · US

Funding

Development of an Assay for the Early Detection of Ovarian CancerR01CA136491 · NCI · WOMEN AND INFANTS HOSPITAL-RHODE ISLAND · PI MOORE, RICHARD G. · 2009 to 2013
$1.9M
NCI NIH HHS R01 CA136491NCI NIH HHS R01 CA136491-01
6 · The paper itself

Abstract

Antiestrogens including tamoxifen and fulvestrant have been evaluated as chemotherapeutics for ovarian cancer, particularly in cases of platinum resistant disease. Human epididymis protein 4 (HE4) is highly overexpressed in women with ovarian cancer and overexpression of HE4 has been found to correlate with platinum resistance. However, the role of HE4 in modulating responses to hormones and hormonal therapy has not been characterized in ovarian cancer. Here we demonstrate that 17β-estradiol, tamoxifen, and fulvestrant induce nuclear and nucleolar translocation of HE4 and that HE4 overexpression induces resistance to antiestrogens. HE4 was found to interact with estrogen receptor-α (ER-α), and HE4 overexpression resulted in ER-α downregulation in vitro and in human ovarian cancers. We identified a novel role for importin-4 in governing the nuclear transport of HE4. Treatment with ivermectin, an importin inhibitor, blocked HE4/importin-4 nuclear accumulation and sensitized HE4-overexpressing ovarian cancer cells to fulvestrant and tamoxifen.

Indexed as

Antineoplastic Agents, HormonalApoptosisBlotting, WesternCell NucleusCell ProliferationDrug Resistance, NeoplasmEstradiolFemaleFluorescent Antibody TechniqueFulvestrantGene Expression Regulation, NeoplasticHumansImmunoenzyme TechniquesImmunoprecipitationKaryopherinsMicroscopy, ConfocalAntineoplastic Agents, HormonalEstradiolFulvestrantKaryopherinsProteinsTamoxifenWAP Four-Disulfide Core Domain Protein 2WFDC2 protein, human

Identifiers

PMID24975515
PMCPMC4074789
OpenAlexW2085391180

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.