Project/Area Number |
23591393
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Hematology
|
Research Institution | Saga University |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
ARAGANE Naoko 佐賀大学, 医学部, 講師 (20321846)
出 勝 佐賀大学, 医学部, 助教 (00398124)
|
Co-Investigator(Renkei-kenkyūsha) |
IDE Masaru 佐賀大学, 医学部, 助教 (00398124)
|
Project Period (FY) |
2011 – 2013
|
Project Status |
Completed (Fiscal Year 2013)
|
Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
|
Keywords | 低酸素応答 / HIF-1 / リンパ腫 / 造血幹細胞 / がん幹細胞 / 薬剤耐性 / Lymphoma / hypoxia / transgenic mouse / BCR-ABL / CML / 低酸素応答遺伝子 / 幹細胞 / アポトーシス |
Research Abstract |
Hypoxia-inducible factor-1alfa (HIF-1 alfa) plays an important role in the induction of various genes under hypoxic condition. We investigate the role of HIF-1 alfa in tumor development and metastasis, and established transgenic mice constitutively expressing HIF-1A gene under regulation of the cytomegalovirus gene promoter. HIF-1 alfa protein levels varied among organs, but the expression of HIF-1 alfa mRNA gradually increased in an age-dependent manner. The transgenic mice developed tumors in the lymphoid, lung, and breast; the most prominent tumor was lymphoma appearing in the intestinal mucosa and intra-mesenchymal tissues. The lymphocytes of the transgenic mice revealed prolonged survival under long-term culture conditions and revealed increased resistance to cytotoxic drugs. These results suggest that HIF-1 alfa play an important role in lymphomagenesis mediated through the prolonged survival of lymphocytes in this transgenic mouse model.
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