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ELF5 and DOK7 regulation in anti-estrogen treated cells and tumors

Overview of attention for article published in Cancer Cell International, February 2016
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Title
ELF5 and DOK7 regulation in anti-estrogen treated cells and tumors
Published in
Cancer Cell International, February 2016
DOI 10.1186/s12935-016-0282-9
Pubmed ID
Authors

Lily M. Fitzgerald, Eva P. Browne, Kevin D. Christie, Elizabeth C. Punska, Leo O. Simmons, Kristin E. Williams, Brian T. Pentecost, Rahul M. Jawale, Christopher N. Otis, Kathleen F. Arcaro

Abstract

Most women with primary breast cancers that express estrogen receptor alpha (ER or ESR1) are treated with endocrine therapies including the anti-estrogen tamoxifen, but resistance to these anti-endocrine therapies often develops. This study characterizes the expression of hormone receptors, and the mRNA and DNA methylation levels of docking protein 7 (DOK7), and E74-like factor 5 (ELF5), in 21 novel tamoxifen-resistant cell lines and extends the findings to primary and recurrent human breast tumors. Twenty-one tamoxifen-selected cell lines were developed through cloning by limiting dilution of an MCF-7 cell culture treated with 1 μM tamoxifen for 6 months. The parent (MCF-7) and tamoxifen-selected cell lines were characterized for protein expression of ER, progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) using immunohistochemistry (IHC). The mRNA levels of ER, DOK7, and ELF5 were assessed using quantitative RT-PCR. Promoter methylation levels of DOK7 and ELF5 were determined by pyrosequencing of bisulfite-modified DNA. The relationship between hormone receptor status and promoter methylation of DOK7 and ELF5 was further examined using available methylation array data (Illumina HM450) from a set of paired primary and second breast tumors from 24 women. All 21 of the novel tamoxifen-selected cell lines are ER-positive, and HER2-negative, and 18 of the cell lines are PR-negative while the MCF-7 cells were scored as ER-positive, modestly PR-positive and HER2 negative. Expression of DOK7 and ELF5 is significantly up-regulated in half of the tamoxifen-selected cell lines as compared to the parental MCF-7. In contrast, the previously established ER-negative TMX2-28 cell line has decreased expression of both DOK7 and ELF5 and increased DNA methylation in the transcriptional start site region of these genes. ELF5 methylation was lower in second versus primary tumors in women who received anti-estrogen treatment, in PR-negative versus PR-positive tumors, and in the subset of PR-positive first tumors from the group of women who had second PR-negative tumors as compared to those who had second PR-positive tumors. The distinct ELF5 methylation of PR-positive primary tumors from women who had a PR-negative recurrence indicates the possibility of stratification of women for tailored treatment in the early stages of disease.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 23 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 23 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 4 17%
Other 3 13%
Student > Postgraduate 3 13%
Student > Doctoral Student 2 9%
Professor > Associate Professor 2 9%
Other 5 22%
Unknown 4 17%
Readers by discipline Count As %
Agricultural and Biological Sciences 5 22%
Medicine and Dentistry 5 22%
Biochemistry, Genetics and Molecular Biology 4 17%
Unspecified 1 4%
Social Sciences 1 4%
Other 3 13%
Unknown 4 17%
Attention Score in Context

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 25 February 2016.
All research outputs
#19,054,237
of 23,613,071 outputs
Outputs from Cancer Cell International
#1,170
of 1,869 outputs
Outputs of similar age
#218,031
of 298,783 outputs
Outputs of similar age from Cancer Cell International
#9
of 17 outputs
Altmetric has tracked 23,613,071 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,869 research outputs from this source. They receive a mean Attention Score of 4.2. This one is in the 23rd percentile – i.e., 23% 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 298,783 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 15th percentile – i.e., 15% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 17 others from the same source and published within six weeks on either side of this one. This one is in the 23rd percentile – i.e., 23% of its contemporaries scored the same or lower than it.