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Hypermethylation and loss of retinoic acid receptor responder 1 expression in human choriocarcinoma

Overview of attention for article published in Journal of Experimental & Clinical Cancer Research, November 2017
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Title
Hypermethylation and loss of retinoic acid receptor responder 1 expression in human choriocarcinoma
Published in
Journal of Experimental & Clinical Cancer Research, November 2017
DOI 10.1186/s13046-017-0634-x
Pubmed ID
Authors

H. Huebner, R. Strick, D. L. Wachter, S. Kehl, P. L. Strissel, R. Schneider-Stock, A. Hartner, W. Rascher, L. C. Horn, M. W. Beckmann, M. Ruebner, F. B. Fahlbusch

Abstract

Human placental development resembles tumorigenesis, due to the invasive and fusogenic potential of trophoblasts. However, these features are tightly controlled in trophoblasts. Disturbance of this spatial and temporal regulation is thought to contribute to the rare formation of choriocarcinomas. Promoter hypermethylation and loss of the tumor suppressor Retinoic acid receptor responder 1 (RARRES1) were shown to contribute to cancer progression. Our study investigated the epigenetic and transcriptional regulation of RARRES1 in healthy human placenta in comparison to choriocarcinoma cell lines and cases. Three choriocarcinoma cell lines (Jeg-3, JAR and BeWo) were treated with three different retinoic acid derivates (Am580, Tazarotene and all-trans retinoic acid) and 5-aza-2'-deoxycytidine. We analyzed RARRES1 promoter methylation by pyrosequencing and performed realtime-PCR quantification to determine RARRES1 expression in placental tissue and trophoblastic cell lines. Additionally, RARRES1 was stained in healthy placentas and in biopsies of choriocarcinoma cases (n = 10) as well as the first trimester trophoblast cell line Swan71 by immunofluorescence and immunohistochemistry. In the choriocarcinoma cell lines, RARRES1 expression could not be induced by sole retinoic acid treatment. Stimulation with 5-aza-2'-deoxycytidine significantly induced RARRES1 expression, which then could be further increased with Am580, Tazarotene and all-trans retinoic acid. In comparison to healthy placenta, choriocarcinoma cell lines showed a hypermethylation of the RARRES1 promoter, which correlated with a reduced RARRES1 expression. In concordance, RARRES1 protein expression was lost in choriocarcinoma tissue. Additionally, in the trophoblastic cell line Swan71, we found a significant induction of RARRES1 expression with increased cell density, during mitosis and in syncytial knots. Our findings showed that RARRES1 expression is absent in choriocarcinoma due to promoter methylation. Based on our analysis, we hypothesize that RARRES1 might exert tumor suppressive functions in multiple cellular processes (e.g. cell cycle regulation, adhesion, invasion and apoptosis).

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 18 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 18 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 4 22%
Student > Ph. D. Student 4 22%
Student > Doctoral Student 1 6%
Lecturer > Senior Lecturer 1 6%
Other 1 6%
Other 1 6%
Unknown 6 33%
Readers by discipline Count As %
Agricultural and Biological Sciences 5 28%
Biochemistry, Genetics and Molecular Biology 3 17%
Nursing and Health Professions 1 6%
Medicine and Dentistry 1 6%
Neuroscience 1 6%
Other 0 0%
Unknown 7 39%
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 27 November 2017.
All research outputs
#15,745,807
of 25,382,440 outputs
Outputs from Journal of Experimental & Clinical Cancer Research
#930
of 2,380 outputs
Outputs of similar age
#243,466
of 445,887 outputs
Outputs of similar age from Journal of Experimental & Clinical Cancer Research
#11
of 42 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,380 research outputs from this source. They receive a mean Attention Score of 4.8. This one has gotten more attention than average, scoring higher than 57% 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 445,887 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 42 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 73% of its contemporaries.