Evidence map›Paper›PMID 21784846›Full record

ArticleThe Journal of biological chemistry2011

Forced expression of heat shock protein 27 (Hsp27) reverses P-glycoprotein (ABCB1)-mediated drug efflux and MDR1 gene expression in Adriamycin-resistant human breast cancer cells.

Ragu Kanagasabai, Karthikeyan Krishnamurthy, Lawrence J Druhan, Govindasamy Ilangovan

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

Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
3.9field-weighted citation impact, top 5% 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

35 citing papers in PubMed, 76 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Revisiting the therapeutic potential of tocotrienol.BioFactors (Oxford, England) · 2022
    Review
  9. Review
  10. Review
  11. Review
  12. Article
  13. Review
  14. Expression of heat shock proteins in adult honey bee (Saudi journal of biological sciences · 2019
    Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. 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

4 authors at 2 institutions in 1 country.

Ragu KanagasabaiDivision of Cardiovascular Medicine, Davis Heart and Lung Research Institute, Department of Internal Medicine, Ohio State University, Columbus, Ohio 43210, USA.
Karthikeyan Krishnamurthy
Lawrence J Druhan
Govindasamy Ilangovan
Lung Institute · USThe Ohio State University · US

Funding

Heat Shock Proteins, Nitric Oxide and Oxygen Consumption in the HeartR01HL078796 · NHLBI · OHIO STATE UNIVERSITY · PI ILANGOVAN, GOVINDASAMY · 2006 to 2009
$1.3M
Role of Heat Shock Factor 1 in Doxorubincin-Induced CardiotoxicityR21HL094881 · NHLBI · OHIO STATE UNIVERSITY · PI ILANGOVAN, GOVINDASAMY · 2010 to 2011
$419k
NHLBI NIH HHS R01 HL078796NHLBI NIH HHS R01 HL078796-02NHLBI NIH HHS R21 HL094881
6 · The paper itself

Abstract

Mutant p53 accumulation has been shown to induce the multidrug resistance gene (MDR1) and ATP binding cassette (ABC)-based drug efflux in human breast cancer cells. In the present work, we have found that transcriptional activation of the oxidative stress-responsive heat shock factor 1 (HSF-1) and expression of heat shock proteins, including Hsp27, which is normally known to augment proteasomal p53 degradation, are inhibited in Adriamycin (doxorubicin)-resistant MCF-7 cells (MCF-7/adr). Such an endogenous inhibition of HSF-1 and Hsp27 in turn results in p53 mutation with gain of function in its transcriptional activity and accumulation in MCF-7/adr. Also, lack of HSF-1 enhances nuclear factor κB (NF-κB) DNA binding activity together with mutant p53 and induces MDR1 gene and P-glycoprotein (P-gp, ABCB1), resulting in a multidrug-resistant phenotype. Ectopic expression of Hsp27, however, significantly depleted both mutant p53 and NF-κB (p65), reversed the drug resistance by inhibiting MDR1/P-gp expression in MCF-7/adr cells, and induced cell death by increased G(2)/M population and apoptosis. We conclude from these results that HSF-1 inhibition and depletion of Hsp27 is a trigger, at least in part, for the accumulation of transcriptionally active mutant p53, which can either directly or NF-κB-dependently induce an MDR1/P-gp phenotype in MCF-7 cells. Upon Hsp27 overexpression, this pathway is abrogated, and the acquired multidrug resistance is significantly abolished so that MCF-7/adr cells are sensitized to Dox. Thus, clinical alteration in Hsp27 or NF-κB level will be a potential approach to circumvent drug resistance in breast cancer.

Indexed as

ATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1Breast NeoplasmsCell DeathCell Line, TumorDNA-Binding ProteinsDoxorubicinDrug Resistance, NeoplasmEnzyme ActivationFemaleGene Expression Regulation, NeoplasticHeat-Shock ProteinsHeat Shock Transcription FactorsHSP27 Heat-Shock ProteinsHumansIntracellular SpaceABCB1 protein, humanATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1DNA-Binding ProteinsDoxorubicinHeat-Shock ProteinsHeat Shock Transcription FactorsHSP27 Heat-Shock ProteinsHSPB1 protein, humanMitogen-Activated Protein KinasesMolecular ChaperonesMutant ProteinsNF-kappa BTranscription FactorsTumor Suppressor Protein p53

Identifiers

PMID21784846
PMCPMC3190913
OpenAlexW2071107415

What OpenQuestion holds

Textmetadata
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.