| Project/Area Number |
14570117
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Shinshu University |
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Principal Investigator |
TAKEOKA Michiko Shinshu University, Graduate School of Medicine, Assistant Researcher, 大学院・医学研究科, 助手 (30197280)
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| Co-Investigator(Kenkyū-buntansha) |
TANIGUCHI Shun'ichiro Shinshu University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (60117166)
EHARA Takashi Shinshu University, School of Medicine, Associate Professor, 医学部, 助教授 (00203646)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2003: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | calponin h1 / actin / truncate / mutation / cancer / motility / calponin / カルポニンh1 / CH domain / Actin binding site / Calponin repeats / C terminal / actin安定性 / HT1080細胞 / truncates |
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| Research Abstract |
To investigate the effects of calponin h1(CNh1) on the cell proliferation and motility, human calponin h1 was transfected to human fibrosarcoma, HT1080. CNh1-transfected cells exhibited flattened morphology with organized actin filaments, significant decrease in cell motility. Anchorage-independent growth and tumorigenicity in nude mice were suppressed in CNh1-transfected cells.
To identify the region of CNh1 that suppresses proliferation and motility, CNh1 consisted of four domains, CHD, actin binding site (ABS), CNrepeats (CNR) and C terminal, were divided to 12 truncates. As a result, the motility was suppressed by the CNR. Since Repeat 1 (R1) of CNR is reported as a second actin binding site, and has targets of protein kinase C (PKC), actin-depolymerization and podosome formation was investigated. Actin-depolymerization was suppressed by the stimulation with cytochalasin D, and formation of podosome was also suppressed with PDBu (PKC stimulator) in CNh1 transfected cells. Truncates that lack ABS or CNR-R1, and mutant that has mutation of S175A and T184A were transfected. In all three transfectants, transverse actin fiber was separated from calponin h1 and podosome formation was facilitated. Calponin h1 is considered to resist cytochalasin D or PDBu by binding to transverse actin fiber in tumor cells.
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