| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Outline of Final Research Achievements |
We found that tumor necrosis factor alpha (TNFα) is required for tumorigenesis of an osteosarcoma cell line, AX cells. AX cells were generated by transducing c-Myc oncogene into Ink4a-deficient mesenchymal stem cells. Transplantation of AX cells into wild-type mouse peritoneal cavity resulted in tumorigenesis leading to mortality within 21 days. We found that TNFα-expressing macrophages were recruited to tumor lesions, and lethal tumor development was not observed in TNFα-deficient mice, suggesting that TNFα is required for tumorigenesis of AX cells. Osteoblastic gene expression was significantly inhibited in AX cells by TNFα, and such inhibition was reversed by addition of either a TNFα-inhibitor or a MEK thereby ERK inhibitor. These results suggest that the undifferentiated state of AX cells was the TNFα-ERK pathway dependent.
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