Anoxia induces macrophage inhibitory cytokine-1 (MIC-1) in glioblastoma cells independently of p53 and HIF-1

摘要: Human astrocytic brain tumors select for mutations in the p53 tumor suppressor gene early malignant progression. is activated upon various kinds of cellular stress leading to apoptosis or cell cycle arrest, but also implicated complex biological processes such as inhibition angiogenesis and metastasis. In an effort shed light on consequences mediated by inactivation gliomas, we established Tet-On system LN-Z308 glioblastoma line. The macrophage inhibitory cytokine-1 (MIC-1) was identified a most prominent target expression profiling. Oxygen deprivation, important stress, revealed MIC-1 anoxia responsive lines. up-regulation through alternative, hypoxia inducible factor 1 (HIF-1) independent pathway. Furthermore, ectopic line completely abolished its inherent tumorigenicity nude mice, while proliferation vitro not affected. present experimental model may exert anti-tumorigenic properties via paracrine mechanism host cells vivo. Taken together, these data suggest that downstream mediator function, acting itself intercessor signaling exerting activities.