Abstract
Several FGFs are able to reduce and improve radiation-induced tissue damage, but there are no reports about whether FGF12 plays a role in radiation sensitivity. In this study, we demonstrated for the first time that FGF12 was expressed in the human leukemic mast cell line HMC-1. The overexpression of FGF12 in HMC-1 cells decreased the ionizing radiation-induced apoptosis, and siRNA-mediated repression of FGF12 expression augmented the apoptosis in HMC-1 cells. In contrast, the mitogen-activated protein kinase (MAPK) scaffold protein islet brain 2 (IB2), which was reported to bind to FGF12, was also expressed in HMC-1 cells, and suppressed radiation-induced apoptosis by itself; however IB2 did not interfere with the anti-apoptotic effect of FGF12. The FGF12-IB2 complex was expected to be involved in the p38 MAPK signaling pathway; however, SB203580 (an inhibitor of p38 MAPK) did not suppress the anti-apoptotic effect of overexpression of FGF12. Instead, FGF12 strongly suppressed the marked augmentation of apoptosis induced by inhibition of the MEK/ERK pathway with PD98059. In addition, the expression of Fgf12 transcripts was detected in murine cultured mast cells, which were derived from bone marrow or fetal skin. These findings suggest that FGF12 suppresses the radiation-induced apoptosis in mast cells independently of IB2.
