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Targeting interferon response genes sensitizes aromatase inhibitor resistant breast cancer cells to estrogen-induced cell death

Overview of attention for article published in Breast Cancer Research, January 2015
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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 (88th percentile)
  • High Attention Score compared to outputs of the same age and source (87th percentile)

Mentioned by

news
1 news outlet
twitter
4 tweeters
facebook
1 Facebook page

Citations

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42 Dimensions

Readers on

mendeley
56 Mendeley
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Title
Targeting interferon response genes sensitizes aromatase inhibitor resistant breast cancer cells to estrogen-induced cell death
Published in
Breast Cancer Research, January 2015
DOI 10.1186/s13058-014-0506-7
Pubmed ID
Authors

Hye Joung Choi, Asona Lui, Joshua Ogony, Rifat Jan, Peter J Sims, Joan Lewis-Wambi

Abstract

IntroductionEstrogen deprivation using aromatase inhibitors (AIs) is currently the standard of care for postmenopausal women with hormone receptor-positive breast cancer. Unfortunately, the majority of patients treated with AIs eventually develop resistance, inevitably resulting in patient relapse and, ultimately, death. The mechanism by which resistance occurs is still not completely known, however, recent studies suggest that impaired/defective interferon signaling might play a role. In the present study, we assessed the functional role of IFITM1 and PLSCR1; two well-known interferon response genes in AI resistance.MethodsReal-time PCR and Western blot analyses were used to assess mRNA and protein levels of IFITM1, PLSCR1, STAT1, STAT2, and IRF-7 in AI-resistant MCF-7:5C breast cancer cells and AI-sensitive MCF-7 and T47D cells. Immunohistochemistry (IHC) staining was performed on tissue microarrays consisting of normal breast tissues, primary breast tumors, and AI-resistant recurrence tumors. Enzyme-linked immunosorbent assay was used to quantitate intracellular IFN¿ level. Neutralizing antibody was used to block type 1 interferon receptor IFNAR1 signaling. Small interference RNA (siRNA) was used to knockdown IFITM1, PLSCR1, STAT1, STAT2, IRF-7, and IFN¿ expression.ResultsWe found that IFITM1 and PLSCR1 were constitutively overexpressed in AI-resistant MCF-7:5C breast cancer cells and AI-resistant tumors and that siRNA knockdown of IFITM1 significantly inhibited the ability of the resistant cells to proliferate, migrate, and invade. Interestingly, suppression of IFITM1 significantly enhanced estradiol-induced cell death in AI-resistant MCF-7:5C cells and markedly increased expression of p21, Bax, and Noxa in these cells. Significantly elevated level of IFN¿ was detected in AI-resistant MCF-7:5C cells compared to parental MCF-7 cells and suppression of IFN¿ dramatically reduced IFITM1 PLSCR1, p-STAT1, and p-STAT2 expression in the resistant cells. Lastly, neutralizing antibody against IFNAR1/2 and knockdown of STAT1/STAT2 completely suppressed IFITM1, PLSCR1, p-STAT1, and p-STAT2 expression in the resistant cells, thus confirming the involvement of the canonical IFN¿ signaling pathway in driving the overexpression of IFITM1 and other interferon-stimulated genes (ISGs) in the resistant cells.ConclusionOverall, these results demonstrate that constitutive overexpression of ISGs enhances the progression of AI-resistant breast cancer and that suppression of IFITM1 and other ISGs sensitizes AI-resistant cells to estrogen-induced cell death.

Twitter Demographics

The data shown below were collected from the profiles of 4 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 56 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 56 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 12 21%
Researcher 9 16%
Student > Bachelor 7 13%
Student > Master 6 11%
Student > Postgraduate 5 9%
Other 5 9%
Unknown 12 21%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 12 21%
Agricultural and Biological Sciences 11 20%
Medicine and Dentistry 9 16%
Pharmacology, Toxicology and Pharmaceutical Science 3 5%
Immunology and Microbiology 3 5%
Other 4 7%
Unknown 14 25%

Attention Score in Context

This research output has an Altmetric Attention Score of 11. 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 19 January 2015.
All research outputs
#1,259,819
of 12,786,466 outputs
Outputs from Breast Cancer Research
#179
of 1,448 outputs
Outputs of similar age
#37,131
of 329,639 outputs
Outputs of similar age from Breast Cancer Research
#5
of 41 outputs
Altmetric has tracked 12,786,466 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 90th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,448 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.0. This one has done well, scoring higher than 87% 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 329,639 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 88% of its contemporaries.
We're also able to compare this research output to 41 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 87% of its contemporaries.