DNA methylation inhibitor causes cell growth retardation and gene expressionchanges in feline lymphoma cells

[摘要] DNA methylation is an epigenetic mechanism controlling gene expression without affectingDNA sequences, and aberrant DNA methylation patterns are features of a number of diseases.Notably, epigenetic errors in cancer cells have been intensively studied over the last twodecades in humans; however, little is known concerning dogs and cats. To analyze DNAmethylation and gene expression changes in feline lymphoma cells, we added the DNAmethylation inhibitor 5-aza-2’-deoxycytidine (5-aza) to three cell lines (3281 and FT-1cells derived from T-cell lymphoma and MS4 cells derived from B-cell lymphoma). Adding5-aza significantly retarded cell growth in a dose-dependent manner in all cell lines, andthere were aberrant gene expression patterns. Transcription factor Sox11expression in 3281 cells was de-repressed by 5-aza treatment, and subsequent promoter DNAdemethylation was analyzed by bisulfite sequencing. Cell cycle analysis suggested thatinhibition of cell growth was due to DNA replication arrest, and this supported the resultof increased expression of p27kip1 gene which disturbed cells of 3281 andFT-1 entering the S phase. In this study, 5-aza suppressed the growth of feline lymphomacells, but further experiments with normal lymph cells are necessary to confirmspecificity of this drug treatment and to expand it for clinical use.

[学科分类] 兽医学

[关键词] 5-aza-2’-deoxycytidine;apoptosis;DNA methylation;feline lymphoma;Sox11