title: FGF-2 inhibits TNF-α mediated apoptosis through upregulation of Bcl2-A1 and Bcl-xL in ATDC5 cells.
abstract: FGF-2 is involved in cell survival, proliferation, apoptosis, and angiogenesis in a wide variety of cells. FRGRs, PI3K and MAP kinases are well known mediators of FGF signaling. Despite its known roles during many developmental processes, including osteogenesis, there are few known targets of FGF-2. In the present study, we identified Bcl2-A1 and Bcl-xL as two prominent targets involved in promoting cell survival. Pretreatment of ATDC5 cells with FGF-2 increased cell survival, while siRNAs specific for Bcl2-A1 and Bcl-xL compromised the anti- apoptotic effect of FGF-2, sensitized the cells to apoptosis triggered by TNF-α. Chemical inhibition of FGFR, NFkB, and PI3K activity by PD173074, pyrrolidine dithiocarbamate, and LY294002 respectively abrogated the FGF-2-mediated induction of Bcl2-A1 and Bcl-xL expression. Taken together, our data demonstrate that a subset of Bcl2 family proteins are the targets of FGF-2 signaling that promotes the survival of ATDC5 cells.
authors.affiliation: Division of Biochemistry, College of Medicine, Chungbuk National University, Cheongju 361-763, Korea.
authors.forename: Hey-Ryun
authors.initials: HR
authors.lastname: Kim
authors.forename: Youn-Moo
authors.initials: YM
authors.lastname: Heo
authors.forename: Kyoung-Il
authors.initials: KI
authors.lastname: Jeong
authors.forename: Yong-Min
authors.initials: YM
authors.lastname: Kim
authors.forename: Hae Lan
authors.initials: HL
authors.lastname: Jang
authors.forename: Kwang-Yeol
authors.initials: KY
authors.lastname: Lee
authors.forename: Chang-Yeol
authors.initials: CY
authors.lastname: Yeo
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Hak-Kyo
authors.initials: HK
authors.lastname: Lee
authors.forename: Seung-Ryul
authors.initials: SR
authors.lastname: Kim
authors.forename: Eung-Gook
authors.initials: EG
authors.lastname: Kim
authors.forename: Joong-Kook
authors.initials: JK
authors.lastname: Choi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology* / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D051379:Mice; D015778:Minor Histocompatibility Antigens; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D051020:bcl-X Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: C096816:BCL2-related protein A1; C494812:Bcl2l1 protein, mouse; D015778:Minor Histocompatibility Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D051020:bcl-X Protein; D016222:Fibroblast Growth Factor 2