부산대학교 도서관

The relationship between schizophrenia (SCZ) and cancer development remains controversial. Based on the disease-geneassociation platform, it has been revealed that tumor necrosis factor receptor (TNFR) could be an important mediatory factorin both cancer and SCZ development. TNF-α also increases the expression of brain-derived neurotrophic factor (BDNF)and tropomyosin receptor kinase B (TrkB) in the development of SCZ and tumor, but the role of TNFR in mediating theassociation between the two diseases remains unclear. We studied the vital roles of TNFR2 in the progression of tumor andSCZ-like behavior using A549 lung cancer cell xenografted TNFR2 knockout mice. TNFR2 knockout mice showed signifi -cantly decreased tumor size and weight as well as schizophrenia-like behaviors compared to wild-type mice. Consistent withthe reduced tumor growth and SCZ-like behaviors, the levels of TrkB and BDNF expression were signifi cantly decreased inthe lung tumor tissues and pre-frontal cortex of TNFR2 knockout mice. However, intravenous injection of BDNF (160 μg/kg) to TNFR2 knockout mice for 4 weeks increased tumor growth and SCZ-like behaviors as well as TrkB expression. Inin vitro study, signifi cantly decreased cell growth and expression of TrkB and BDNF by siTNFR2 transfection were found inA549 lung cancer cells. However, the addition of BDNF (100 ng/ml) into TNFR2 siRNA transfected A549 lung cancer cellsrecovered cell growth and the expression of TrkB. These results suggest that TNFR2 could be an important factor in mediatingthe comorbidity between lung tumor growth and SCZ development through increased TrkB-dependent BDNF levels.