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Molecular characterization of irinotecan (SN-38) resistant human breast cancer cell lines

Overview of attention for article published in BMC Cancer, January 2016
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Title
Molecular characterization of irinotecan (SN-38) resistant human breast cancer cell lines
Published in
BMC Cancer, January 2016
DOI 10.1186/s12885-016-2071-1
Pubmed ID
Authors

Haatisha Jandu, Kristina Aluzaite, Louise Fogh, Sebastian Wingaard Thrane, Julie B. Noer, Joanna Proszek, Khoa Nguyen Do, Stine Ninel Hansen, Britt Damsgaard, Signe Lykke Nielsen, Magnus Stougaard, Birgitta R. Knudsen, José Moreira, Petra Hamerlik, Madhavsai Gajjar, Marcel Smid, John Martens, John Foekens, Yves Pommier, Nils Brünner, Anne-Sofie Schrohl, Jan Stenvang

Abstract

Studies in taxane and/or anthracycline refractory metastatic breast cancer (mBC) patients have shown approximately 30 % response rates to irinotecan. Hence, a significant number of patients will experience irinotecan-induced side effects without obtaining any benefit. The aim of this study was to lay the groundwork for development of predictive biomarkers for irinotecan treatment in BC. We established BC cell lines with acquired or de novo resistance to SN-38, by exposing the human BC cell lines MCF-7 and MDA-MB-231 to either stepwise increasing concentrations over 6 months or an initial high dose of SN-38 (the active metabolite of irinotecan), respectively. The resistant cell lines were analyzed for cross-resistance to other anti-cancer drugs, global gene expression, growth rates, TOP1 and TOP2A gene copy numbers and protein expression, and inhibition of the breast cancer resistance protein (ABCG2/BCRP) drug efflux pump. We found that the resistant cell lines showed 7-100 fold increased resistance to SN-38 but remained sensitive to docetaxel and the non-camptothecin Top1 inhibitor LMP400. The resistant cell lines were characterized by Top1 down-regulation, changed isoelectric points of Top1 and reduced growth rates. The gene and protein expression of ABCG2/BCRP was up-regulated in the resistant sub-lines and functional assays revealed BCRP as a key mediator of SN-38 resistance. Based on our preclinical results, we suggest analyzing the predictive value of the BCRP in breast cancer patients scheduled for irinotecan treatment. Moreover, LMP400 should be tested in a clinical setting in breast cancer patients with resistance to irinotecan.

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X Demographics

The data shown below were collected from the profiles of 3 X users 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 79 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 79 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 16 20%
Student > Bachelor 13 16%
Student > Master 11 14%
Student > Ph. D. Student 6 8%
Student > Postgraduate 4 5%
Other 11 14%
Unknown 18 23%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 24 30%
Agricultural and Biological Sciences 13 16%
Medicine and Dentistry 8 10%
Pharmacology, Toxicology and Pharmaceutical Science 4 5%
Engineering 4 5%
Other 6 8%
Unknown 20 25%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 April 2016.
All research outputs
#15,357,612
of 23,613,071 outputs
Outputs from BMC Cancer
#3,797
of 8,487 outputs
Outputs of similar age
#224,220
of 398,366 outputs
Outputs of similar age from BMC Cancer
#88
of 199 outputs
Altmetric has tracked 23,613,071 research outputs across all sources so far. This one is in the 32nd percentile – i.e., 32% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,487 research outputs from this source. They receive a mean Attention Score of 4.4. This one has gotten more attention than average, scoring higher than 50% 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 398,366 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 40th percentile – i.e., 40% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 199 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 52% of its contemporaries.