Evidence map›Paper›PMID 25632947›Full record

ArticleBMC cancer2015

TOX3 is expressed in mammary ER(+) epithelial cells and regulates ER target genes in luminal breast cancer.

Akop Seksenyan, Asha Kadavallore, Ann E Walts, Brian de la Torre, Dror Berel, Samuel P Strom, Parinaz Aliahmad, Vincent A Funari, Jonathan Kaye

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

Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 2 pooled it
2.1field-weighted citation impact, top 14% 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

23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 46 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. The TOX subfamily: all-round players in the immune system.Clinical and experimental immunology · 2022
    Review
  9. Risk Association ofCurrent oncology (Toronto, Ont.) · 2022
    Article
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  11. Article
  12. Article
  13. Frontiers in endocrinology · 2020
    Article
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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

9 authors at 1 institution in 1 country.

Akop SeksenyanResearch Division of Immunology, Departments of Biomedical Sciences and Medicine, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Davis 5089, Los Angeles, 90048, CA, USA. Akop.Seksenyan@my.rosalindfranklin.edu.
Asha KadavalloreResearch Division of Immunology, Departments of Biomedical Sciences and Medicine, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Davis 5089, Los Angeles, 90048, CA, USA. Kadavallorea@csmc.edu.
Ann E WaltsDepartment of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Ann.Walts@cshs.org.
Brian de la TorreResearch Division of Immunology, Departments of Biomedical Sciences and Medicine, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Davis 5089, Los Angeles, 90048, CA, USA. Delatorreb@csmc.edu.
Dror BerelSamuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. berel@usc.edu.
Samuel P StromGenomics Core Facility, Cedars-Sinai Medical Center, Los Angeles, CA, USA. SStrom@mednet.ucla.edu.
Parinaz AliahmadResearch Division of Immunology, Departments of Biomedical Sciences and Medicine, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Davis 5089, Los Angeles, 90048, CA, USA. Aliahmadp@csmc.edu.
Vincent A FunariGenomics Core Facility, Cedars-Sinai Medical Center, Los Angeles, CA, USA. FunariV@cshs.org.
Jonathan KayeResearch Division of Immunology, Departments of Biomedical Sciences and Medicine, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Davis 5089, Los Angeles, 90048, CA, USA. kayej@csmc.edu.
Cedars-Sinai Medical Center · US

Funding

UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1TR000124
6 · The paper itself

Abstract

backgroundA breast cancer susceptibility locus has been mapped to the gene encoding TOX3. Little is known regarding the expression pattern or biological role of TOX3 in breast cancer or in the mammary gland. Here we analyzed TOX3 expression in murine and human mammary glands and in molecular subtypes of breast cancer, and assessed its ability to alter the biology of breast cancer cells.

methodsWe used a cell sorting strategy, followed by quantitative real-time PCR, to study TOX3 gene expression in the mouse mammary gland. To study the expression of this nuclear protein in human mammary glands and breast tumors, we generated a rabbit monoclonal antibody specific for human TOX3. In vitro studies were performed on MCF7, BT474 and MDA-MB-231 cell lines to study the effects of TOX3 modulation on gene expression in the context of breast cancer cells.

resultsWe found TOX3 expression in estrogen receptor-positive mammary epithelial cells, including progenitor cells. A subset of breast tumors also highly expresses TOX3, with poor outcome associated with high expression of TOX3 in luminal B breast cancers. We also demonstrate the ability of TOX3 to alter gene expression in MCF7 luminal breast cancer cells, including cancer relevant genes TFF1 and CXCR4. Knockdown of TOX3 in a luminal B breast cancer cell line that highly expresses TOX3 is associated with slower growth. Surprisingly, TOX3 is also shown to regulate TFF1 in an estrogen-independent and tamoxifen-insensitive manner.

conclusionsThese results demonstrate that high expression of this protein likely plays a crucial role in breast cancer progression. This is in sharp contrast to previous studies that indicated breast cancer susceptibility is associated with lower expression of TOX3. Together, these results suggest two different roles for TOX3, one in the initiation of breast cancer, potentially related to expression of TOX3 in mammary epithelial cell progenitors, and another role for this nuclear protein in the progression of cancer. In addition, these results can begin to shed light on the reported association of TOX3 expression and breast cancer metastasis to the bone, and point to TOX3 as a novel regulator of estrogen receptor-mediated gene expression.

Indexed as

Gene Expression Regulation, NeoplasticAnimalsApoptosis Regulatory ProteinsBreast NeoplasmsCell Line, TumorCell MovementDisease Models, AnimalEpithelial CellsFemaleGene Expression ProfilingHigh Mobility Group ProteinsHumansInsulin-Like Growth Factor ILigandsMammary Glands, HumanMiceApoptosis Regulatory ProteinsHigh Mobility Group ProteinsInsulin-Like Growth Factor ILigandsReceptors, EstrogenReceptors, ProgesteroneTOX3 protein, humanTrans-Activators

Identifiers

PMID25632947
PMCPMC4324787
OpenAlexW2087125879

What OpenQuestion holds

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LicenceCC BY
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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.