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, andangiogenesis in a wide variety of cells. FRGRs, PI3K and MAPkinases are well known mediators of FGF signaling. Despite itsknown roles during many developmental processes, includingosteogenesis, there are few known targets of FGF-2. In thepresent study, we identified Bcl2-A1 and Bcl-xL as two prominenttargets involved in promoting cell survival. Pretreatmentof ATDC5 cells with FGF-2 increased cell survival, whilesiRNAs specific for Bcl2-A1 and Bcl-xL compromised the anti-apoptotic effect of FGF-2, sensitized the cells to apoptosistriggered by TNF-α. Chemical inhibition of FGFR, NFkB, andPI3K activity by PD173074, pyrrolidine dithiocarbamate, andLY294002 respectively abrogated the FGF-2-mediated inductionof Bcl2-A1 and Bcl-xL expression. Taken together, our datademonstrate that a subset of Bcl2 family proteins are the targetsof FGF-2 signaling that promotes the survival of ATDC5cells. [BMB reports 2012; 45(5): 287-292]

Keywords

• Apoptosis
• ATDC5 cells
• Bcl-xL
• Bcl2-A1
• FGF-2
• TNF-α