title: Methylation status of theFHITgene in the transformed human mesenchymal F6 stem cell line.
abstract: The fragile histidine triad (FHIT) gene is known to be a tumor suppressor gene and the abnormal methylation ofFHIThas been identified in leukemia and several solid tumors. The transformation of the tumor F6 cell line from human fetal mesenchymal stem cells (FMSCs) was first reported in a previous study that also identified the presence of a population of cancer stem cells in the F6 cell line. However, the existence of the epigenetic changes during the transformation process have yet to be elucidated. To confirm the role of theFHITgene in the transformation process of FMSC, the expression level and methylation status of theFHITgene was examined in F6 tumor cells and FMSCs. Additionally, the alteration in cell morphology, the cell cycle and apoptosis in F6 cells following 5-Aza-CdR treatment was assessed. It was found that theFHITgene was expressed in FMSCs, but not in F6 cells. The methylation-specific PCR results demonstrated that the promoter methylation ofFHITgenes existed in the F6 cell line. Subsequent to treatment with 5-Aza-CdR the expression ofFHITgenes was restored in F6 cells. In addition, the morphology of F6 cells was altered, and the cell cycle was arrested in the G2phase, with the initiation of apoptosis. Overall, the present findings demonstrated that theFHITgene was methylated in F6 cells and demethylation treatment lead to changes in the biological characteristics, thereby promoting the apoptosis of F6 cells.FHITgene methylation may be one of the molecular events involved in the development and transformation of FMSCs into F6 tumor cells.
authors.affiliation: Department of Laboratory Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Xue-Jing
authors.initials: XJ
authors.lastname: Xu
authors.affiliation: Department of Laboratory Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Gao
authors.affiliation: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.affiliation: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Qian
authors.affiliation: Department of Laboratory Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Guang-Yu
authors.initials: GY
authors.lastname: Gu
authors.affiliation: Department of Laboratory Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Kui
authors.initials: K
authors.lastname: Zhang
authors.affiliation: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Wen-Rong
authors.initials: WR
authors.lastname: Xu
keywords: DNA methylation; F6 cells; fetal mesenchymal stem cells; fragile histidine triad