Sonic hedgehog signaling protects @entity1 XXXX cells against ionizing radiation in an autocrine manner.

@entity1 @entity1161 @entity8889 @entity4851 @entity23902 @entity157 @entity2750
PURPOSE: Sonic hedgehog ( @entity4851 ) signaling is critical to embryogenesis and resistance to chemotherapy. We aimed to examine the role of @entity4851 signaling in the response to radiation of @entity1 @entity157 ( @entity157 ) cells. METHODS AND MATERIALS: Response to ionizing @entity1161 ( @entity1161 ) was evaluated by clonogenic assay. Quantitative @entity1161 -polymerase chain reaction for @entity2750 ( @entity2750 ) expression was performed. Cytosolic accumulation of @entity4851 and nuclear translocation of @entity8889 were assessed by immunofluorescence. @entity8889 knockdown was done by RNA interference (RNAi). Immunoprecipitation was performed to detect @entity4851 ligand in conditioned medium. Immunofluorescent stain for y-H2AX was used as an index of DNA double strand breaks (DSB). Expression of proteins related to DNA damage repair was assessed by Western blotting. RESULTS: We found that @entity4851 ligand could protect @entity1 @entity157 HA22T and Sk-Hep1 cells against @entity1161 . In HA22T cells, @entity4851 ligand activated the @entity4851 signaling with upregulation of @entity4851 , @entity2750 , and @entity8889 expression. The nuclear translocation of @entity8889 further supports the activation of @entity8889 . The radioprotection by @entity4851 ligand was partly blocked by @entity4851 antibody neutralization and was abolished by @entity8889 RNAi, suggesting a critical role of @entity4851 signaling in radiation resistance. Furthermore, we noted that soluble factors secreted into conditioned medium, either constitutively or responding to radiation, by HA22T or Sk-Hep1 cells protected subsequent culturing cells against @entity1161 . Immunoprecipitation shows the presence of @entity4851 peptide in conditioned medium. Intriguingly, antibody neutralization of @entity4851 ligand or knockdown of @entity8889 reversed the radioprotective effect of conditioned medium. Furthermore, @entity4851 ligand reduced the @entity1161 -induced phosphorylation of @entity23902 and impaired the repair of DNA DSB. CONCLUSIONS: Activation of @entity4851 signaling protects @entity157 cells against ionizing radiation in an autocrine manner. Impairment of DNA damage repair might involve mechanism of @entity4851 -induced radioresistance. Targeting @entity4851 signaling pathway may be a novel strategy to enhance the radioresponse of @entity1 @entity157 cells.
