Evidence map›Paper›PMID 28460457›Full record

ArticleOncotarget2017

The vitamin D receptor is involved in the regulation of human breast cancer cell growth via a ligand-independent function in cytoplasm.

Trupti Trivedi, Yu Zheng, Pierrick G J Fournier, Sreemala Murthy, Sutha John, Suzanne Schillo, Colin R Dunstan, Khalid S Mohammad, Hong Zhou, Markus J Seibel and 1 more

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

Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
1.7field-weighted citation impact, top 17% 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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.

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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

11 authors at 4 institutions in 3 countries.

Trupti TrivediBone Research Program, ANZAC Research Institute, University of Sydney, Sydney, Australia.
Yu ZhengBone Research Program, ANZAC Research Institute, University of Sydney, Sydney, Australia.
Pierrick G J FournierDivision of Endocrinology, Department of Medicine, Indiana University-Purdue University at Indianapolis, Indianapolis, Indiana, USA.
Sreemala MurthyDivision of Endocrinology, Department of Medicine, Indiana University-Purdue University at Indianapolis, Indianapolis, Indiana, USA.
Sutha JohnDivision of Endocrinology, Department of Medicine, Indiana University-Purdue University at Indianapolis, Indianapolis, Indiana, USA.
Suzanne SchilloBone Research Program, ANZAC Research Institute, University of Sydney, Sydney, Australia.
Colin R DunstanDepartment of Biomedical Engineering, University of Sydney, Sydney, Australia.
Khalid S MohammadDivision of Endocrinology, Department of Medicine, Indiana University-Purdue University at Indianapolis, Indianapolis, Indiana, USA.
Hong ZhouBone Research Program, ANZAC Research Institute, University of Sydney, Sydney, Australia.
Markus J SeibelBone Research Program, ANZAC Research Institute, University of Sydney, Sydney, Australia.
Theresa A GuiseDivision of Endocrinology, Department of Medicine, Indiana University-Purdue University at Indianapolis, Indianapolis, Indiana, USA.
Indiana University – Purdue University Indianapolis · USUniversity of Sydney · AUAnzac Research Institute · AUCenter for Scientific Research and Higher Education at Ensenada · MX

Funding

TGFbeta IN THE BONE MICROENVIRONMENT: ROLE IN TUMOR METASTASISR01CA069158 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI GUISE, THERESA A · 2001 to 2012
$2.8M
Differential TGF-Beta Signaling in Bone Microenviroment: Impact on Tumor GrowthU01CA143057 · NCI · INDIANA UNIVERSITY INDIANAPOLIS · PI BHOWMICK, NEIL A., GUISE, THERESA A · 2011 to 2015
$2.7M
NCI NIH HHS R01 CA069158NCI NIH HHS U01 CA143057
6 · The paper itself

Abstract

Vitamin D has pleiotropic effects on multiple tissues, including malignant tumors. Vitamin D inhibits breast cancer growth through activation of the vitamin D receptor (VDR) and via classical nuclear signaling pathways. Here, we demonstrate that the VDR can also function in the absence of its ligand to control behaviour of human breast cancer cells both outside and within the bone microenvironment. Stable shRNA expression was used to knock down VDR expression in MCF-7 cells, generating two VDR knockdown clonal lines. In ligand-free culture, knockdown of VDR in MCF-7 cells significantly reduced proliferation and increased apoptosis, suggesting that the VDR plays a ligand-independent role in cancer cell growth. Implantation of these VDR knockdown cells into the mammary fat pad of nude mice resulted in reduced tumor growth in vivo compared with controls. In the intra-tibial xenograft model, VDR knockdown greatly reduced the ability of the cells to form tumors in the bone microenvironment. The in vitro growth of VDR knockdown cells was rescued by the expression of a mutant form of VDR which is unable to translocate to the nucleus and hence accumulates in the cytoplasm. Thus, our data indicate that in the absence of ligand, the VDR promotes breast cancer growth both in vitro and in vivo and that cytoplasmic accumulation of VDR is sufficient to produce this effect in vitro. This new mechanism of VDR action in breast cancer cells contrasts the known anti-proliferative nuclear actions of the VDR-vitamin D ligand complex.

Indexed as

AnimalsApoptosisBone NeoplasmsBreast NeoplasmsCell Line, TumorCell ProliferationCytoplasmDisease Models, AnimalFemaleGene ExpressionGene Knockdown TechniquesHeterograftsHumansLigandsMiceMutationLigandsReceptors, CalcitriolVDR protein, humanVitamin Dbone metastasisbreast cancerligand independentvitamin Dvitamin D receptor

Identifiers

PMID28460457
PMCPMC5432290
OpenAlexW2592464148

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.