Evidence map›Paper›PMID 26576332›Full record

ArticleSpringerPlus2015

Altered regulation of PDK4 expression promotes antiestrogen resistance in human breast cancer cells.

William Walter, Jennifer Thomalla, Josh Bruhn, Dedra H Fagan, Cheryl Zehowski, Douglas Yee, Andrew Skildum

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

Article in SpringerPlus, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.2field-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

22 citing papers in PubMed, 32 citations in OpenAlex.

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  14. Expression and clinical significance of PDK family in breast cancer based on data mining.International journal of clinical and experimental pathology · 2021
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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

7 authors at 2 institutions in 1 country.

William WalterDepartment of Biomedical Sciences, University of Minnesota Medical School, Duluth Campus, Duluth, MN USA.
Jennifer ThomallaDepartment of Biomedical Sciences, University of Minnesota Medical School, Duluth Campus, Duluth, MN USA.
Josh BruhnDepartment of Biomedical Sciences, University of Minnesota Medical School, Duluth Campus, Duluth, MN USA.
Dedra H FaganMasonic Cancer Center, University of Minnesota, Minneapolis, MN USA.
Cheryl ZehowskiDepartment of Biomedical Sciences, University of Minnesota Medical School, Duluth Campus, Duluth, MN USA.
Douglas YeeMasonic Cancer Center, University of Minnesota, Minneapolis, MN USA.
Andrew SkildumDepartment of Biomedical Sciences, University of Minnesota Medical School, Duluth Campus, Duluth, MN USA ; Masonic Cancer Center, University of Minnesota, Minneapolis, MN USA.
University of Minnesota, Duluth · USUniversity of Minnesota Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Acquired or de novo resistance to the selective estrogen receptor modulators tamoxifen and fulvestrant (ICI) is a major barrier to successful treatment of breast cancer. Gene expression patterns in tamoxifen resistant (TamR-MCF-7) cells were compared to their parental cells (MCF-7L) to identify an aberrantly regulated metabolic pathway. TamR-MCF-7 cells are cross resistant to ICI and doxorubicin, and have increased mitochondrial DNA. A small subset of genes had altered expression in TamR-MCF-7 relative to MCF-7L cells. One of the genes, pyruvate dehydrogenase kinase-4 (PDK4), phosphorylates pyruvate dehydrogenase (PDH). PDK4 expression was elevated in TamR-MCF-7 cells; this result was also observed in a second model of acquired antiestrogen resistance. PDK4 expression is controlled in part by glucocorticoid response elements in the PDK4 gene promoter. In MCF-7L cells, PDK4 mRNA expression was insensitive to glucocorticoid receptor agonists, while dexamethasone dramatically increased PDK4 expression in TamR-MCF-7 cells. Using siRNA to knock down PDK4 expression increased TamR-MCF-7 sensitivity to ICI; in contrast adapting cells to growth in glucose depleted media did not affect ICI sensitivity. Despite TamR-MCF-7 cells high levels of PDK4 mRNA relative to MCF-7L, TamR-MCF-7 cells have increased PDH activity. Wild type MCF-7 cells are reported to be heterozygous for a G to A mutation that results in a substitution of threonine for alanine near PDK4's catalytic site. We found loss of heterozygosity in TamR-MCF-7 cells; TamR-MCF-7 are homozygous for the wild type allele. These data support a role for altered regulation of PDH by PDK4 and altered substrate utilization in the development of drug resistance in human breast cancer cells.

Indexed as

Antiestrogen resistanceBreast cancerGlucoseMetabolismPyruvate dehydrogenase kinase-isoform 4 (PDK4)

Identifiers

PMID26576332
PMCPMC4641142
OpenAlexW2152602101

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.