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Acquisition of docetaxel resistance in breast cancer cells reveals upregulation of ABCB1 expression as a key mediator of resistance accompanied by discrete upregulation of other specific genes and…

Overview of attention for article published in Tumor Biology, January 2015
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  • High Attention Score compared to outputs of the same age and source (82nd percentile)

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Title
Acquisition of docetaxel resistance in breast cancer cells reveals upregulation of ABCB1 expression as a key mediator of resistance accompanied by discrete upregulation of other specific genes and pathways
Published in
Tumor Biology, January 2015
DOI 10.1007/s13277-015-3072-4
Pubmed ID
Authors

Stine Ninel Hansen, David Westergaard, Mathilde Borg Houlberg Thomsen, Mette Vistesen, Khoa Nguyen Do, Louise Fogh, Kirstine C. Belling, Jun Wang, Huanming Yang, Ramneek Gupta, Henrik J. Ditzel, José Moreira, Nils Brünner, Jan Stenvang, Anne-Sofie Schrohl

Abstract

The microtubule-targeting taxanes are important in breast cancer therapy, but no predictive biomarkers have yet been identified with sufficient scientific evidence to allow clinical routine use. The purposes of the present study were to develop a cell-culture-based discovery platform for docetaxel resistance and thereby identify key molecular mechanisms and predictive molecular characteristics to docetaxel resistance. Two docetaxel-resistant cell lines, MCF7RES and MDARES, were generated from their respective parental cell lines MCF-7 and MDA-MB-231 by stepwise selection in docetaxel dose increments over 15 months. The cell lines were characterized regarding sensitivity to docetaxel and other chemotherapeutics and subjected to transcriptome-wide mRNA microarray profiling. MCF7RES and MDARES exhibited a biphasic growth inhibition pattern at increasing docetaxel concentrations. Gene expression analysis singled out ABCB1, which encodes permeability glycoprotein (Pgp), as the top upregulated gene in both MCF7RES and MDARES. Functional validation revealed Pgp as a key resistance mediator at low docetaxel concentrations (first-phase response), whereas additional resistance mechanisms appeared to be prominent at higher docetaxel concentrations (second-phase response). Additional resistance mechanisms were indicated by gene expression profiling, including genes in the interferon-inducible protein family in MCF7RES and cancer testis antigen family in MDARES. Also, upregulated expression of various ABC transporters, ECM-associated proteins, and lysosomal proteins was identified in both resistant cell lines. Finally, MCF7RES and MDARES presented with cross-resistance to epirubicin, but only MDARES showed cross-resistance to oxaliplatin. In conclusion, Pgp was identified as a key mediator of resistance to low docetaxel concentrations with other resistance mechanisms prominent at higher docetaxel concentrations. Supporting Pgp upregulation as one major mechanism of taxane resistance and cell-line-specific alterations as another, both MCF7RES and MDARES were cross-resistant to epirubicin (Pgp substrate), but only MDARES was cross-resistant to oxaliplatin (non-Pgp substrate).

X Demographics

X Demographics

The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 58 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Iran, Islamic Republic of 1 2%
Unknown 57 98%

Demographic breakdown

Readers by professional status Count As %
Student > Master 14 24%
Student > Bachelor 9 16%
Student > Ph. D. Student 8 14%
Researcher 6 10%
Professor > Associate Professor 3 5%
Other 8 14%
Unknown 10 17%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 20 34%
Medicine and Dentistry 10 17%
Agricultural and Biological Sciences 10 17%
Pharmacology, Toxicology and Pharmaceutical Science 3 5%
Computer Science 2 3%
Other 3 5%
Unknown 10 17%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 28 December 2023.
All research outputs
#7,879,000
of 25,223,158 outputs
Outputs from Tumor Biology
#393
of 2,663 outputs
Outputs of similar age
#101,374
of 364,087 outputs
Outputs of similar age from Tumor Biology
#29
of 175 outputs
Altmetric has tracked 25,223,158 research outputs across all sources so far. This one has received more attention than most of these and is in the 67th percentile.
So far Altmetric has tracked 2,663 research outputs from this source. They receive a mean Attention Score of 2.5. This one has done well, scoring higher than 84% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 364,087 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 71% of its contemporaries.
We're also able to compare this research output to 175 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 82% of its contemporaries.