↓ Skip to main content

Downregulation of histone H2A and H2B pathways is associated with anthracycline sensitivity in breast cancer

Overview of attention for article published in Breast Cancer Research, January 2016
Altmetric Badge

About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (89th percentile)
  • Good Attention Score compared to outputs of the same age and source (71st percentile)

Mentioned by

news
1 news outlet
twitter
6 tweeters

Citations

dimensions_citation
19 Dimensions

Readers on

mendeley
75 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Downregulation of histone H2A and H2B pathways is associated with anthracycline sensitivity in breast cancer
Published in
Breast Cancer Research, January 2016
DOI 10.1186/s13058-016-0676-6
Pubmed ID
Authors

Marsela Braunstein, Linda Liao, Nicola Lyttle, Nazleen Lobo, Karen J Taylor, Paul M Krzyzanowski, Irina Kalatskaya, Cindy Q Yao, Lincoln D Stein, Paul C Boutros, Christopher J Twelves, Richard Marcellus, John MS Bartlett, Melanie Spears, Braunstein, Marsela, Liao, Linda, Lyttle, Nicola, Lobo, Nazleen, Taylor, Karen J, Krzyzanowski, Paul M, Kalatskaya, Irina, Yao, Cindy Q, Stein, Lincoln D, Boutros, Paul C, Twelves, Christopher J, Marcellus, Richard, Bartlett, John M S, Spears, Melanie, Karen J. Taylor, Paul M. Krzyzanowski, Cindy Q. Yao, Lincoln D. Stein, Paul C. Boutros, Christopher J. Twelves, John M. S. Bartlett

Abstract

Drug resistance in breast cancer is the major obstacle to effective treatment with chemotherapy. While upregulation of multidrug resistance genes is an important component of drug resistance mechanisms in vitro, their clinical relevance remains to be determined. Therefore, identifying pathways that could be targeted in the clinic to eliminate anthracycline-resistant breast cancer remains a major challenge. We generated paired native and epirubicin-resistant MDA-MB-231, MCF7, SKBR3 and ZR-75-1 epirubicin-resistant breast cancer cell lines to identify pathways contributing to anthracycline resistance. Native cell lines were exposed to increasing concentrations of epirubicin until resistant cells were generated. To identify mechanisms driving epirubicin resistance, we used a complementary approach including gene expression analyses to identify molecular pathways involved in resistance, and small-molecule inhibitors to reverse resistance. In addition, we tested its clinical relevance in a BR9601 adjuvant clinical trial. Characterisation of epirubicin-resistant cells revealed that they were cross-resistant to doxorubicin and SN-38 and had alterations in apoptosis and cell-cycle profiles. Gene expression analysis identified deregulation of histone H2A and H2B genes in all four cell lines. Histone deacetylase small-molecule inhibitors reversed resistance and were cytotoxic for epirubicin-resistant cell lines, confirming that histone pathways are associated with epirubicin resistance. Gene expression of a novel 18-gene histone pathway module analysis of the BR9601 adjuvant clinical trial revealed that patients with low expression of the 18-gene histone module benefited from anthracycline treatment more than those with high expression (hazard ratio 0.35, 95 % confidence interval 0.13-0.96, p = 0.042). This study revealed a key pathway that contributes to anthracycline resistance and established model systems for investigating drug resistance in all four major breast cancer subtypes. As the histone modification can be targeted with small-molecule inhibitors, it represents a possible means of reversing clinical anthracycline resistance. ClinicalTrials.gov identifier NCT00003012 . Registered on 1 November 1999.

Twitter Demographics

The data shown below were collected from the profiles of 6 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 75 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Spain 1 1%
Unknown 74 99%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 17 23%
Researcher 11 15%
Student > Master 11 15%
Student > Bachelor 9 12%
Student > Doctoral Student 4 5%
Other 11 15%
Unknown 12 16%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 18 24%
Medicine and Dentistry 14 19%
Agricultural and Biological Sciences 9 12%
Pharmacology, Toxicology and Pharmaceutical Science 3 4%
Nursing and Health Professions 3 4%
Other 11 15%
Unknown 17 23%

Attention Score in Context

This research output has an Altmetric Attention Score of 13. 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 15 February 2016.
All research outputs
#548,687
of 7,196,678 outputs
Outputs from Breast Cancer Research
#84
of 934 outputs
Outputs of similar age
#33,874
of 319,984 outputs
Outputs of similar age from Breast Cancer Research
#11
of 39 outputs
Altmetric has tracked 7,196,678 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 92nd percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 934 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.0. This one has done particularly well, scoring higher than 91% 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 319,984 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 89% of its contemporaries.
We're also able to compare this research output to 39 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 71% of its contemporaries.