Evidence map›Paper›PMID 28677036›Full record

ArticleCellular oncology (Dordrecht, Netherlands)2017

ΔNp73 regulates the expression of the multidrug-resistance genes ABCB1 and ABCB5 in breast cancer and melanoma cells - a short report.

Habib A M Sakil, Marina Stantic, Johanna Wolfsberger, Suzanne Egyhazi Brage, Johan Hansson, Margareta T Wilhelm

Open access · hybridAbstract read
In one paragraph

Article in Cellular oncology (Dordrecht, Netherlands), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.6field-weighted citation impact, top 30% 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

9 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
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  6. Review
  7. TAp73 represses NF-κB-mediated recruitment of tumor-associated macrophages in breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2021
    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

6 authors at 1 institution in 1 country.

Habib A M SakilDepartment of Microbiology, Tumor and Cell biology (MTC), Karolinska Institutet, 171 77, Stockholm, Sweden.
Marina StanticDepartment of Microbiology, Tumor and Cell biology (MTC), Karolinska Institutet, 171 77, Stockholm, Sweden.
Johanna WolfsbergerDepartment of Microbiology, Tumor and Cell biology (MTC), Karolinska Institutet, 171 77, Stockholm, Sweden.
Suzanne Egyhazi BrageDepartment of Oncology-Pathology, Karolinska Institutet, 171 76, Stockholm, Sweden.
Johan HanssonDepartment of Oncology-Pathology, Karolinska Institutet, 171 76, Stockholm, Sweden.
Margareta T WilhelmDepartment of Microbiology, Tumor and Cell biology (MTC), Karolinska Institutet, 171 77, Stockholm, Sweden. Margareta.Wilhelm@ki.se.ORCID http://orcid.org/0000-0002-0516-9724
Karolinska Institutet · SE

Funding

Cancerfonden 150574Cancerfonden CAN 2016/823Knut och Alice Wallenbergs Stiftelse KAW 2013.0093Radiumhemmets Forskningsfonder 144073Stockholms Läns Landsting Dnr LS 2015-1198Vetenskapsrådet 2016-02386
6 · The paper itself

Abstract

purposeMultidrug resistance (MDR) is a major cause of treatment failure. In cancer cells, MDR is often caused by an increased efflux of therapeutic drugs mediated by an up-regulation of ATP binding cassette (ABC) transporters. It has previously been shown that oncogenic ΔNp73 plays an important role in chemo-resistance. Here we aimed at unraveling the role of ΔNp73 in regulating multidrug resistance in breast cancer and melanoma cells.

methodsKEGG pathway analysis was used to identify pathways enriched in breast cancer samples with a high ΔNp73 expression. We found that the ABC transporter pathway was most enriched. The expression of selected ABC transporters was analyzed using qRT-PCR upon siRNA/shRNA-mediated knockdown or exogenous overexpression of ΔNp73 in the breast cancer-derived cell lines MCF7 and MDA-MB-231, as well as in primary melanoma samples and in the melanoma-derived cell line SK-MEL-28. The ability to efflux doxorubicin and the concomitant effects on cell proliferation were assessed using flow cytometry and WST-1 assays.

resultsWe found that high ΔNp73 levels correlate with a general up-regulation of ABC transporters in breast cancer samples. In addition, we found that exogenous expression of ΔNp73 led to an increase in the expression of ABCB1 and ABCB5 in the breast cancer-derived cell lines tested, while knocking down of ΔNp73 resulted in a reduction in ABCB1 and ABCB5 expression. In addition, we found that ΔNp73 reduction leads to an intracellular retention of doxorubicin in MDA-MB-231 and MCF7 cells and a concomitant decrease in cell proliferation. The effect of ΔNp73 on ABCB5 expression was further confirmed in metastases from melanoma patients and in the melanoma-derived cell line SK-MEL-28.

conclusionsOur data support a role for ΔNp73 in the multidrug-resistance of breast cancer and melanoma cells.

Indexed as

ATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1Blotting, WesternBreast NeoplasmsCell Line, TumorCell ProliferationDoxorubicinDrug Resistance, NeoplasmFemaleGene Expression Regulation, NeoplasticHumansMCF-7 CellsMelanomaReal-Time Polymerase Chain ReactionTumor Protein p73ABCB1 protein, humanABCB5 protein, humanATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1DoxorubicinTumor Protein p73ABC transportersBreast cancerMelanomaMulti-drug resistance genesp53 familyp73

Identifiers

PMID28677036
PMCPMC5705756
OpenAlexW2733779122

What OpenQuestion holds

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Registered trials

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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.