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Aurora kinase B is important for antiestrogen resistant cell growth and a potential biomarker for tamoxifen resistant breast cancer

Overview of attention for article published in BMC Cancer, April 2015
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Mentioned by

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2 tweeters

Citations

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19 Dimensions

Readers on

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44 Mendeley
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Title
Aurora kinase B is important for antiestrogen resistant cell growth and a potential biomarker for tamoxifen resistant breast cancer
Published in
BMC Cancer, April 2015
DOI 10.1186/s12885-015-1210-4
Pubmed ID
Authors

Sarah L Larsen, Christina W Yde, Anne-Vibeke Laenkholm, Birgitte B Rasmussen, Anne Katrine Duun-Henriksen, Martin Bak, Anne E Lykkesfeldt, Tove Kirkegaard

Abstract

Resistance to antiestrogen therapy is a major clinical challenge in the treatment of estrogen receptor α (ER)-positive breast cancer. The aim of the study was to explore the growth promoting pathways of antiestrogen resistant breast cancer cells to identify biomarkers and novel treatment targets. Antiestrogen sensitive and resistant T47D breast cancer cell lines were used as model systems. Parental and fulvestrant resistant cell lines were subjected to a kinase inhibitor library. Kinase inhibitors preferentially targeting growth of fulvestrant resistant cells were identified and the growth inhibitory effect verified by dose-response cell growth experiments. Protein expression and phosphorylation were investigated by western blot analysis. Cell cycle phase distribution and cell death were analyzed by flow cytometry. To evaluate Aurora kinase B as a biomarker for endocrine resistance, immunohistochemistry was performed on archival primary tumor tissue from breast cancer patients who have received adjuvant endocrine treatment with tamoxifen. The selective Aurora kinase B inhibitor barasertib was identified to preferentially inhibit growth of fulvestrant resistant T47D breast cancer cell lines. Compared with parental cells, phosphorylation of Aurora kinase B was higher in the fulvestrant resistant T47D cells. Barasertib induced degradation of Aurora kinase B, caused mitotic errors, and induced apoptotic cell death as measured by accumulation of SubG1 cells and PARP cleavage in the fulvestrant resistant cells. Barasertib also exerted preferential growth inhibition of tamoxifen resistant T47D cell lines. Finally, high percentage of Aurora kinase B positive tumor cells was significantly associated with reduced disease-free and overall survival in 261 ER-positive breast cancer patients, who have received tamoxifen as first-line adjuvant endocrine treatment. Our results indicate that Aurora kinase B is a driving factor for growth of antiestrogen resistant T47D breast cancer cell lines, and a biomarker for reduced benefit of tamoxifen treatment. Thus, inhibition of Aurora kinase B, e.g. with the highly selective kinase inhibitor barasertib, could be a candidate new treatment for breast cancer patients with acquired resistance to antiestrogens.

Twitter Demographics

The data shown below were collected from the profiles of 2 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 44 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 2%
Unknown 43 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 11 25%
Student > Bachelor 7 16%
Researcher 7 16%
Student > Master 4 9%
Student > Doctoral Student 4 9%
Other 6 14%
Unknown 5 11%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 11 25%
Medicine and Dentistry 9 20%
Agricultural and Biological Sciences 7 16%
Chemistry 2 5%
Veterinary Science and Veterinary Medicine 1 2%
Other 6 14%
Unknown 8 18%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 08 May 2015.
All research outputs
#7,762,274
of 12,372,945 outputs
Outputs from BMC Cancer
#2,229
of 4,558 outputs
Outputs of similar age
#122,468
of 225,794 outputs
Outputs of similar age from BMC Cancer
#5
of 12 outputs
Altmetric has tracked 12,372,945 research outputs across all sources so far. This one is in the 23rd percentile – i.e., 23% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,558 research outputs from this source. They receive a mean Attention Score of 3.9. This one is in the 41st percentile – i.e., 41% of its peers scored the same or lower than it.
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 225,794 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 35th percentile – i.e., 35% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 12 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 50% of its contemporaries.