| Project/Area Number |
23790802
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Gastroenterology
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| Research Institution | Nagoya City University |
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Principal Investigator |
MIZUSHIMA Takashi 名古屋市立大学, 医学(系)研究科(研究院), 研究員 (60433223)
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| Research Collaborator |
尾関 啓司 名古屋市立大学, 大学院医学研究科・臨床, 研究医
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | IBD / colitic cancer / AT1R / ARB / telmisarn / telmisartan / NF-κB |
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| Research Abstract |
It is known that a disintegrin and metalloproteinase (ADAM) cleaves pro-heparin-binding epidermal growth factor-like growth factor (proHB-EGF), and the soluble HB-EGF activates EGFR. Simultaneously, the C-terminal fragment of proHB-EGF (HB-EGF-CTF) translocates into the inner nuclear membrane, and subsequently influences cell proliferation by binding nuclear promyelocytic leukemia zinc finger (PLZF) protein, a transcriptional repressor, which induces its nuclear export.
We found that colon cancer cell proliferation is regulated via the nuclear translocation of HB-EGF C-terminal fragments. And we also found that telmisartan and its derivatives with biphenyl tetrazole completely blocked this association. We propose that the inhibition of HB-EGF-CTF nuclear translocation with telmisartan and its derivatives may lead to novel strategies that prevent cell proliferation in the development of colon cancer.
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