ムラガキ　ヨシヒロ   MURAGAKI Yoshihiro   村垣　善浩    所属   医学部 医学科（東京女子医科大学病院）    職種   客員教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Nerve growth factor induces apoptosis in human medulloblastoma cell lines that express TrkA receptors
掲載誌名	正式名：Journal of Neuroscience 略　 称：J Neurosci ISSNコード：02706474
巻・号・頁	17(2),pp.530-542
著者・共著者	MURAGAKI Yoshihiro†, CHOU Thomas T. , KAPLAN David R. , TROJANOWSKI John Q. , LEE Virginia M.-Y
担当区分	筆頭著者
発行年月	1997/01
概要	Neurotrophins act through their cognate receptors to promote the differentiation and/or survival of neuronal progenitor cells, immature neurons, and other cells. Here, we examined the effects of nerve growth factor (NGF) and its cognate receptor (Trk or TrkA) on the survival of a common childhood brain tumor, i.e., medulloblastoma, a tumor that resembles CNS neuroepithelial progenitor cells. To do this, we engineered two human medulloblastoma cell lines (i.e., D283MED and DAOY cells) to express human TrkA using a retroviral expression vector. Surprisingly, NGF-treated medulloblastoma cells expressing the TrkA receptor (D283trk and DAOYtrk cells) grown in the presence or absence of serum underwent massive apoptosis, but similar treatment did not induce apoptosis in wild-type uninfected cells, cells expressing an empty vector, or cells expressing the TrkC receptor. Furthermore, D283MED cells engineered to express the human p75 NGF receptor (D283p75) also did not undergo apoptosis. Significantly, NGF-induced apoptosis in D283trk and DAOYtrk cells can be inhibited by anti-NGF antibodies and by K-252a, an inhibitor of TrkA tyrosine phosphorylation and mimicked by high concentrations of NT3. Because NGF treatment primarily eliminated D283trk cells from the S phase of the cell cycle, this form of NGF-mediated apoptosis is cell cycle-dependent. These findings suggest that a NGF/TrkA signal transduction pathway could activate apoptotic cell death programs in CNS neuroepithelial progenitor cells and in childhood brain tumors.
DOI	0.1523/JNEUROSCI.17-02-00530.1997
文献番号	8987776