ArticleBMC molecular biology2014
Expression of GBGT1 is epigenetically regulated by DNA methylation in ovarian cancer cells.
Article in BMC molecular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- Exploration of gene presence/absence variations inOpen biology · 2025Article
- A Novel Glycosyltransferase-Related Gene Signature for Overall Survival Prediction in Patients with Ovarian Cancer.International journal of general medicine · 2021Article
- A first genetic linage map construction and QTL mapping for growth traits in Larimichthys polyactis.Scientific reports · 2020Article
- MicroRNA-654-5p suppresses ovarian cancer development impacting on MYC, WNT and AKT pathways.Oncogene · 2019Article
- Methylation and ovarian cancer: Can DNA methylation be of diagnostic use?Molecular and clinical oncology · 2019Review
- Epigenetic Biomarkers in the Management of Ovarian Cancer: Current Prospectives.Frontiers in cell and developmental biology · 2019Review
- Epigenetic modification of α-The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2018Article
- Tissue glycomics distinguish tumour sites in women with advanced serous adenocarcinoma.Molecular oncology · 2017Article
- Epigenetic activation of MGAT3 and corresponding bisecting GlcNAc shortens the survival of cancer patients.Oncotarget · 2016Article
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe GBGT1 gene encodes the globoside alpha-1,3-N-acetylgalactosaminyltransferase 1. This enzyme catalyzes the last step in the multi-step biosynthesis of the Forssman (Fs) antigen, a pentaglycosyl ceramide of the globo series glycosphingolipids. While differential GBGT1 mRNA expression has been observed in a variety of human tissues being highest in placenta and ovary, the expression of GBGT1 and the genes encoding the glycosyltransferases and glycosidases involved in the biosynthesis of Fs as well as the possible involvement of DNA methylation in transcriptional regulation of GBGT1 expression have not yet been investigated.
resultsRT-qPCR profiling showed high GBGT1 expression in normal ovary surface epithelial (HOSE) cell lines and low GBGT1 expression in all (e.g. A2780, SKOV3) except one (OVCAR3) investigated ovarian cancer cell lines, a finding that was confirmed by Western blot analysis. Hierarchical cluster analysis showed that GBGT1 was even the most variably expressed gene of Fs biosynthesis-relevant glycogenes and among the investigated cell lines, whereas NAGA which encodes the alpha-N-acetylgalactosaminidase hydrolyzing Fs was not differentially expressed. Bisulfite- and COBRA-analysis of the CpG island methylation status in the GBGT1 promoter region demonstrated high or intermediate levels of GBGT1 DNA methylation in all ovarian cancer cell lines (except for OVCAR3) but marginal levels of DNA methylation in the two HOSE cell lines. The extent of DNA methylation inversely correlated with GBGT1 mRNA and protein expression. Bioinformatic analysis of GBGT1 in The Cancer Genome Atlas ovarian cancer dataset demonstrated that this inverse correlation was also found in primary ovarian cancer tissue samples confirming our cell line-based findings. Restoration of GBGT1 mRNA and protein expression in low GBGT1-expressing A2780 cells was achieved by 5-aza-2'-deoxycytidine treatment and these treated cells exhibited increased helix pomatia agglutinin-staining, reflecting the elevated presence of Fs disaccharide on these cells.
conclusionsGBGT1 expression is epigenetically silenced through promoter hypermethylation in ovarian cancer. Our findings not only suggest an involvement of DNA methylation in the synthesis of Fs antigen but may also explain earlier studies showing differential GBGT1 expression in various human tissue samples and disease stages.
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