Expression of syncytin in leukemia and lymphoma cells

Sun, Yi; Ouyang, Dong-Yun; Pang, Wei; Tu, Yuan-Quan; Li, Yuye; Shen, Xiaomei; Tam, Siu-Cheung; Yang, Huajun; Zheng, Yong‐Tang

doi:10.1016/j.leukres.2010.03.016

Cited by 29 publications

(28 citation statements)

References 38 publications

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“…The placenta-specific ERVW-1 env gene Syncytin-1 is essential for cell fusion of VCT to the multinucleated SCT in human placentae [31], [32]. Recently Syncytin-1 expression was found in leukaemia and lymphoma cell lines and blood samples [33], but also in other tumours like colorectal, breast and endometrial cancer [34]–[36]. The promoter region of ERVW-1 comprises the 5′LTR of the provirus and the upstream regulatory region (URE) with the trophoblast specific enhancer (TSE) [37], [38] where many factors can regulate Syncytin-1 expression.…”

Section: Introductionmentioning

confidence: 99%

Reduced Syncytin-1 Expression Levels in Placental Syndromes Correlates with Epigenetic Hypermethylation of the ERVW-1 Promoter Region

et al. 2013

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Terminal differentiation of villous cytotrophoblasts (CT) ends in formation of the multinucleated syncytiotrophoblast representing the fetal-maternal interface. Aberrations during this cell-fusion process are associated with Intrauterine Growth Restriction (IUGR), Preeclampsia (PE) and High Elevated Liver and Low Platelets (HELLP) Syndrome. Syncytin-1, the envelope gene of the human Endogenous Retrovirus ERVW-1, is one of the most important genes involved in cell-fusion and showed decreased gene expression during these pathological pregnancies. The aim of this study was to determine the methylation pattern of the entire promoter of ERVW-1 and to correlate these findings with the expression profile of Syncytin-1 in the placental syndromes. 14 isolated villous cytotrophoblasts from control (n = 3), IUGR (n = 3), PE (n = 3), PE/IUGR (n = 3) and HELLP/IUGR (n = 2) placentae were used to determine the mean methylation level (ML) for the ERVW-1 promoter region. ML rose significantly from 29% in control CTs to 49% in IUGR, 53% in PE, 47% in PE/IUGR and 64% in HELLP/IUGR indicating an epigenetic down-regulation of Syncytin-1 by promoter hypermethylation. DNA demethylation of the trophoblast like cell lines BeWo, JEG-3 and JAR with 5-AZA-2′desoxycytidine (AZA) showed an increased Syncytin-1 expression and fusion ability in all cell lines. Promoter activity of the 5′LTR could be inhibited by hypermethylation 42-fold using a luciferase based reporter-gene assay. Finally overexpression of the methyltransferases DNMT3a and LSH could be responsible for a decreased Syncytin-1 expression by promoter hypermethylation of ERVW-1. Our study linked decreased Syncytin-1 expression to an epigenetic hypermethylation of the entire promoter of ERVW-1. Based on our findings we are predicting a broad aberrant epigenetic DNA-methylation pattern in pathological placentae affecting placentogenesis, but also the development of the fetus and the mother during pregnancy.

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Section: Introductionmentioning

confidence: 99%

Reduced Syncytin-1 Expression Levels in Placental Syndromes Correlates with Epigenetic Hypermethylation of the ERVW-1 Promoter Region

et al. 2013

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“…The Syncytin-1 and Syncytin-2 envelope glycoproteins are encoded by full-length HERV sequences belonging to the HERV-W and HERV-FRD families, respectively and, through cell differentiation mechanisms, these proteins are presumably essential for human placentation (reviewed in [11]). Syncytin-1 is also associated with epithelial cancers [12], [13] and was recently detected in the peripheral blood of leukemia and lymphoma patients [14]. Among the HERV-K HML-2 family, full-length proviruses can encode either Rec or Np9 proteins, which are known to interact with cellular partners and ultimately may affect cancer signaling pathways [15], [16], [17], [18].…”

Section: Introductionmentioning

confidence: 99%

Microarray-Based Sketches of the HERV Transcriptome Landscape

Pérot

Mugnier²,

Montgiraud

et al. 2012

PLoS ONE

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Human endogenous retroviruses (HERVs) are spread throughout the genome and their long terminal repeats (LTRs) constitute a wide collection of putative regulatory sequences. Phylogenetic similarities and the profusion of integration sites, two inherent characteristics of transposable elements, make it difficult to study individual locus expression in a large-scale approach, and historically apart from some placental and testis-regulated elements, it was generally accepted that HERVs are silent due to epigenetic control. Herein, we have introduced a generic method aiming to optimally characterize individual loci associated with 25-mer probes by minimizing cross-hybridization risks. We therefore set up a microarray dedicated to a collection of 5,573 HERVs that can reasonably be assigned to a unique genomic position. We obtained a first view of the HERV transcriptome by using a composite panel of 40 normal and 39 tumor samples. The experiment showed that almost one third of the HERV repertoire is indeed transcribed. The HERV transcriptome follows tropism rules, is sensitive to the state of differentiation and, unexpectedly, seems not to correlate with the age of the HERV families. The probeset definition within the U3 and U5 regions was used to assign a function to some LTRs (i.e. promoter or polyA) and revealed that (i) autonomous active LTRs are broadly subjected to operational determinism (ii) the cellular gene density is substantially higher in the surrounding environment of active LTRs compared to silent LTRs and (iii) the configuration of neighboring cellular genes differs between active and silent LTRs, showing an approximately 8 kb zone upstream of promoter LTRs characterized by a drastic reduction in sense cellular genes. These gathered observations are discussed in terms of virus/host adaptive strategies, and together with the methods and tools developed for this purpose, this work paves the way for further HERV transcriptome projects.

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“…The reason for this is that syncytin-1 is known to be up-regulated in multiple sclerosis (30)(31)(32) and a variety of cancers (33,34), including lymphoma and leukaemia (35). It is also known to promote the fusion of malignant cells, both to themselves and normal endothelial cells which contributes to enhanced genetic instability (15,16,34) and recent work has shown that mutations in the HERV-W genomic 3'-long terminal repeat induce up-regulation of syncytin-1 expression in urothelial cell carcinoma (36).…”

Section: Discussionmentioning

confidence: 99%

Silver nanoparticles exhibit size-dependent differential toxicity and induce expression of syncytin-1 in FA-AML1 and MOLT-4 leukaemia cell lines

Alqahtani

Promtong

Oliver

et al. 2016

MUTAGE

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Human endogenous retrovirus (HERV) sequences make up approximately 8% of the human genome and increased expression of some HERV proteins has been observed in various pathologies including leukaemia and multiple sclerosis (MS). However, little is known about the function of these HERV proteins or environmental factors which regulate their expression. Silver nanoparticles (AgNPs) are used very extensively as antimicrobials and antivirals in numerous consumer products although their effect on the expression of HERV gene products is unknown. Cell proliferation and cell toxicity assays were carried out on human acute T lymphoblastic leukaemia (MOLT-4) and Fanconi anaemia associated acute myeloid leukaemia (FA-AML1) cells treated with two different sizes of AgNPs (7 nm and 50 nm diameter). RT-PCR and Western blotting were then used to the assess expression of HERV-W syncytin-1 mRNA and protein in these cells. FA-AML1 cells were more sensitive overall than MOLT-4 to treatment with the smaller 7 nm sized AgNp's being the most toxic in these cells. MOLT-4 cell were more resistant and showed no evidence of differential toxicity to the different sized particles. Syncytin-1 mRNA and protein were induced by both 7 and 50 nm AgNPs in both cell types yet with different kinetics. In summary, the observation that AgNPs induce expression of syncytin-1 in FA-AML1 and MOLT-4 cells at doses as little as 5 µg/ml is grounds for concern since this protein is up-regulated in both malignant and neurodegenerative diseases. Considering the widespread use of AgNPs in the environment it is clear that their ability to induce syncytin-1 should be investigated further in other cell types.3

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Expression of syncytin in leukemia and lymphoma cells

Cited by 29 publications

References 38 publications

Reduced Syncytin-1 Expression Levels in Placental Syndromes Correlates with Epigenetic Hypermethylation of the ERVW-1 Promoter Region

Reduced Syncytin-1 Expression Levels in Placental Syndromes Correlates with Epigenetic Hypermethylation of the ERVW-1 Promoter Region

Microarray-Based Sketches of the HERV Transcriptome Landscape

Silver nanoparticles exhibit size-dependent differential toxicity and induce expression of syncytin-1 in FA-AML1 and MOLT-4 leukaemia cell lines

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