↓ Skip to main content

Everolimus downregulates estrogen receptor and induces autophagy in aromatase inhibitor-resistant breast cancer cells

Overview of attention for article published in BMC Cancer, July 2016
Altmetric Badge

About this Attention Score

  • Average Attention Score compared to outputs of the same age
  • Good Attention Score compared to outputs of the same age and source (71st percentile)

Mentioned by

twitter
6 X users

Citations

dimensions_citation
56 Dimensions

Readers on

mendeley
63 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
Everolimus downregulates estrogen receptor and induces autophagy in aromatase inhibitor-resistant breast cancer cells
Published in
BMC Cancer, July 2016
DOI 10.1186/s12885-016-2490-z
Pubmed ID
Authors

Asona Lui, Jacob New, Joshua Ogony, Sufi Thomas, Joan Lewis-Wambi

Abstract

mTOR inhibition of aromatase inhibitor (AI)-resistant breast cancer is currently under evaluation in the clinic. Everolimus/RAD001 (Afinitor®) has had limited efficacy as a solo agent but is projected to become part of combination therapy for AI-resistant breast cancer. This study was conducted to investigate the anti-proliferative and resistance mechanisms of everolimus in AI-resistant breast cancer cells. In this study we utilized two AI-resistant breast cancer cell lines, MCF-7:5C and MCF-7:2A, which were clonally derived from estrogen receptor positive (ER+) MCF-7 breast cancer cells following long-term estrogen deprivation. Cell viability assay, colony formation assay, cell cycle analysis and soft agar anchorage-independent growth assay were used to determine the efficacy of everolimus in inhibiting the proliferation and tumor forming potential of MCF-7, MCF-7:5C, MCF-7:2A and MCF10A cells. Confocal microscopy and transmission electron microscopy were used to evaluate LC3-II production and autophagosome formation, while ERE-luciferase reporter, Western blot, and RT-PCR analyses were used to assess ER expression and transcriptional activity. Everolimus inhibited the proliferation of MCF-7:5C and MCF-7:2A cells with relatively equal efficiency to parental MCF-7 breast cancer cells. The inhibitory effect of everolimus was due to G1 arrest as a result of downregulation of cyclin D1 and p21. Everolimus also dramatically reduced estrogen receptor (ER) expression (mRNA and protein) and transcriptional activity in addition to the ER chaperone, heat shock protein 90 protein (HSP90). Everolimus restored 4-hydroxy-tamoxifen (4OHT) sensitivity in MCF-7:5C cells and enhanced 4OHT sensitivity in MCF-7 and MCF-7:2A cells. Notably, we found that autophagy is one method of everolimus insensitivity in MCF-7 breast cancer cell lines. This study provides additional insight into the mechanism(s) of action of everolimus that can be used to enhance the utility of mTOR inhibitors as part of combination therapy for AI-resistant breast cancer.

X Demographics

X Demographics

The data shown below were collected from the profiles of 6 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 63 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 63 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 10 16%
Researcher 9 14%
Student > Master 8 13%
Student > Doctoral Student 6 10%
Student > Bachelor 3 5%
Other 8 13%
Unknown 19 30%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 21 33%
Agricultural and Biological Sciences 7 11%
Medicine and Dentistry 4 6%
Pharmacology, Toxicology and Pharmaceutical Science 3 5%
Psychology 3 5%
Other 4 6%
Unknown 21 33%
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 14 August 2016.
All research outputs
#13,475,674
of 22,880,691 outputs
Outputs from BMC Cancer
#2,979
of 8,325 outputs
Outputs of similar age
#192,408
of 356,439 outputs
Outputs of similar age from BMC Cancer
#70
of 264 outputs
Altmetric has tracked 22,880,691 research outputs across all sources so far. This one is in the 39th percentile – i.e., 39% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,325 research outputs from this source. They receive a mean Attention Score of 4.3. This one has gotten more attention than average, scoring higher than 62% 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 356,439 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 44th percentile – i.e., 44% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 264 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.