title: Secreted phospholipases A₂are differentially expressed and epigenetically silenced in human breast cancer cells.
abstract: Secreted phospholipases A2 (sPLA2s) have recently been associated with several cancers, but their role in breast cancer is unknown. Here we demonstrate that mRNA expression of group IIA, III and X sPLA2s differs both in vivo in tumour biopsies and in breast cancer cells in vitro. Their expression is differentially regulated by DNA methylation and histone acetylation and, significantly, all three genes are silenced in aggressive triple negative cells due to both mechanisms. The transcription start site promoter region and the upstream CpG islands, exclusive to the group X sPLA2 gene, have variable roles in the regulation of sPLA2 expression. Our results suggest that the differential expression of hGIIA, hGIII and hGX sPLA2s in breast cancer cells is a consequence of various degrees of epigenetic silencing due to DNA hypermethylation and histone deacetylation.
authors: Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Ljubljana, Slovenia.
authors: Vesna
authors: V
authors: Brglez
authors: Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Ljubljana, Slovenia.
authors: Anja
authors: A
authors: Pucer
authors: Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Ljubljana, Slovenia.
authors: Jože
authors: J
authors: Pungerčar
authors: Institut de Pharmacologie Moléculaire et Cellulaire, CNRS et Université de Nice Sophia Antipolis, UMR 6097, Sophia Antipolis, Valbonne, France.
authors: Gérard
authors: G
authors: Lambeau
authors: Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Ljubljana, Slovenia. Electronic address: toni.petan@ijs.si.
authors: Toni
authors: T
authors: Petan
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D054501:Group II Phospholipases A2 / Q000235:genetics* / Q000378:metabolism; D054520:Group III Phospholipases A2 / Q000235:genetics* / Q000378:metabolism; D054509:Group X Phospholipases A2 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D061986:MCF-7 Cells; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D006877:Hydroxamic Acids; C012589:trichostatin A; D000077209:Decitabine; D054501:Group II Phospholipases A2; D054520:Group III Phospholipases A2; D054509:Group X Phospholipases A2; D001374:Azacitidine
keywords: Breast cancer; DNA methylation; Epigenetics; Histone acetylation; Lipid signalling; Secreted phospholipase A(2)