Assessment of PDGFRβ promoter methylation in canine osteosarcoma using methylation-sensitive high-resolution melting analysis.
CpG Islands
DNA methylation
MS-HRM
PDGF receptor beta
dogs
osteosarcoma
Journal
Veterinary and comparative oncology
ISSN: 1476-5829
Titre abrégé: Vet Comp Oncol
Pays: England
ID NLM: 101185242
Informations de publication
Date de publication:
Dec 2020
Dec 2020
Historique:
received:
24
05
2019
revised:
08
01
2020
accepted:
09
01
2020
pubmed:
18
1
2020
medline:
25
8
2021
entrez:
18
1
2020
Statut:
ppublish
Résumé
Platelet-derived growth factor signalling pathways play a fundamental role in inducing and sustaining the proliferative and prosurvival stimuli in canine osteosarcomas (cOSAs). The increased expression of platelet-derived growth factor receptors (PDGFRs) α and β, and their cognate ligands, were almost invariably observed in cOSAs and OSA-derived cell lines. In particular, overexpression of PDGFRβ-mediated signalling pathways was found in both the tumour microenvironment, where it drives stromal cell recruitment, and in neoangiogenesis, such as in tumour cells where it triggers aberrant proliferation, migration and local invasion. The majority of the pathological consequences of PDGFRβ signalling are because of aberrant expression. In fact, epigenetic dysregulation of oncogenes throughout demethylation of their promoter has emerged as a pivotal mechanism driving oncogenesis. The aim of this study was to assess the methylation status of the PDGFRβ promoter and to clarify its role in modulating the expression of the tyrosine kinase receptor in canine osteosarcoma. The CpG island of the PDGFRβ promoter was identified using a mixed in silico and experimental approach, and a method based upon the methylation-sensitive high-resolution melting assay for quantitatively and precisely assessing the methylation status of the promoter was then set up. The method herein described was then exploited to assess the methylation status of the promoter in a case series of cOSAa. COSAs consistently but variably expressed PDGFRβ. However, the promoter was almost completely demethylated, and its methylation status did not correlate with the expression levels. This finding supported the hypothesis that post-transcriptional regulatory mechanisms may act in cOSAs.
Substances chimiques
Protein-Tyrosine Kinases
EC 2.7.10.1
Receptor, Platelet-Derived Growth Factor beta
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
484-493Subventions
Organisme : Università di Bologna
ID : RFO 2012
Informations de copyright
© 2020 John Wiley & Sons Ltd.
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