A Novel Cyclophane Compound, CPPy, Facilitates NGF-Induced TrkA Signal Transduction and Induces Cell Differentiation in Neuroblastoma(Molecular and Cell Biology)
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概要
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Neuroblastoma (NB) often causes spontaneously regression, and can mature to ganglioneuroma. The form with the most favorable prognosis expresses high levels of TrkA, a high-affinity receptor for nerve growth factor (NGF), whereas advanced NB and associated cell lines have abnormalities in the NGF/TrkA signaling pathway. A novel cyclophane, cyclophane pyridine (CPPy), was designed to conserve the tyrosine phosphorylation of TrkA, thereby enhancing NGF/TrkA signal transduction. We investigated whether this compound improved NGF-induced tyrosine phosphorylation of the Y490 domain of TrkA and conserved the expression of an early gene (c-fos) in human NB cell lines (IMR-32 and NB-39). As determined by Western blotting, TrkA (Y490) phosphorylation was enhanced by the combination of CPPy (10^<-8>M) and NGF (100ng/ml) compared with NGF alone. CPPy also conserved NGF-induced c-fos mRNA expression. Moreover, CPPy induced the morphological differentiation of NB cells, leading to expression of the neuronal marker gene GAP-43. These data suggest that CPPy can induce the differentiation of NB cell lines by facilitating NGF-induced TrkA/Ras/MAPK signal transduction, and may therefore be an effective therapeutic agent for NB.
- 社団法人日本薬学会の論文
- 2007-04-01
著者
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Tabata Keiichi
日本大学 薬学部臨床医学ユニット
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Suzuki T
Department Of Biochemistry University Of Shizuoka School Of Pharmaceutical Sciences:core Research Fo
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YAMAGUCHI Yusuke
Clinical Pharmacy, College of Pharmacy, Nihon University
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TABATA Keiichi
Clinical Pharmacy, College of Pharmacy, Nihon University
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ASAMI Satoru
Clinical Pharmacy, College of Pharmacy, Nihon University
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MIYAKE Muneharu
Medicinal Chemistry, College of Pharmacy, Nihon University
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SuzuKi Takashi
Clinical Pharmacy, College of Pharmacy, Nihon University
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Suzuki T
Department Of Pharmaceutics College Of Pharmacy Nihon University
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Suzuki Takashi
School Of Pharmacy Nihon Univ.
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ASAMI Satoru
Research Unit of Clinical Medicine, College of Pharmacy, Nihon University
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Miyake Muneharu
Medicinal Chemistry College Of Pharmacy Nihon University
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Asami Satoru
Research Unit Of Clinical Medicine College Of Pharmacy Nihon University
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Suganuma Taiyo
(pressent Address)department Of Pharmacology Tokyo Women's Medical University
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Suzuki Takashi
Department Of Biochemistry University Of Shizuoka School Of Pharmaceutical Sciences:core Research Fo
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Yamaguchi Yusuke
Clinical Pharmacy College Of Pharmacy Nihon University
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Tabata Keiichi
School Of Pharmacy Nihon University
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Takase S
College Of Science And Technology (funabashi Campus) Nihon University
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Suzuki Takashi
Clinical And Biotechnology Business Unit Shimadzu Corporation
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