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Retinoic acid-induced apoptosis of the CHP134 neuroblastoma cell line is associated with nuclear accumulation of p53 and is rescued by the GDNF/Ret signal

2001; Alan R. Liss, Inc.; Volume: 36; Issue: 1 Linguagem: Inglês

10.1002/1096-911x(20010101)36

1096-911X

Naoyuki Takada, Eriko Isogai, Takemasa Kawamoto, H. Nakanishi, Satoru Todo, Akira Nakagawara,

Cell death mechanisms and regulation

Medical and Pediatric OncologyVolume 36, Issue 1 p. 122-126 Retinoic acid-induced apoptosis of the CHP134 neuroblastoma cell line is associated with nuclear accumulation of p53 and is rescued by the GDNF/Ret signal Naoyuki Takada MD, PhD, Naoyuki Takada MD, PhD Division of Biochemistry, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuoh-ku, Chiba 260-8717, Japan First Department of Surgery, Hokkaido University School of Medicine, Kita-ku, Sapporo 060-8638, JapanSearch for more papers by this authorEriko Isogai PhD, Eriko Isogai PhD Division of Biochemistry, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuoh-ku, Chiba 260-8717, JapanSearch for more papers by this authorTakemasa Kawamoto MD, Takemasa Kawamoto MD Division of Biochemistry, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuoh-ku, Chiba 260-8717, JapanSearch for more papers by this authorHiroko Nakanishi MD, Hiroko Nakanishi MD Division of Biochemistry, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuoh-ku, Chiba 260-8717, JapanSearch for more papers by this authorSatoru Todo MD, PhD, Satoru Todo MD, PhD First Department of Surgery, Hokkaido University School of Medicine, Kita-ku, Sapporo 060-8638, JapanSearch for more papers by this authorAkira Nakagawara MD, PhD, Corresponding Author Akira Nakagawara MD, PhD akiranak@chiba-cc.pref.chiba.jp Division of Biochemistry, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuoh-ku, Chiba 260-8717, JapanDivision of Biochemistry, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuoh-ku, Chiba 260-8717, JapanSearch for more papers by this author Naoyuki Takada MD, PhD, Naoyuki Takada MD, PhD Division of Biochemistry, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuoh-ku, Chiba 260-8717, Japan First Department of Surgery, Hokkaido University School of Medicine, Kita-ku, Sapporo 060-8638, JapanSearch for more papers by this authorEriko Isogai PhD, Eriko Isogai PhD Division of Biochemistry, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuoh-ku, Chiba 260-8717, JapanSearch for more papers by this authorTakemasa Kawamoto MD, Takemasa Kawamoto MD Division of Biochemistry, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuoh-ku, Chiba 260-8717, JapanSearch for more papers by this authorHiroko Nakanishi MD, Hiroko Nakanishi MD Division of Biochemistry, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuoh-ku, Chiba 260-8717, JapanSearch for more papers by this authorSatoru Todo MD, PhD, Satoru Todo MD, PhD First Department of Surgery, Hokkaido University School of Medicine, Kita-ku, Sapporo 060-8638, JapanSearch for more papers by this authorAkira Nakagawara MD, PhD, Corresponding Author Akira Nakagawara MD, PhD akiranak@chiba-cc.pref.chiba.jp Division of Biochemistry, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuoh-ku, Chiba 260-8717, JapanDivision of Biochemistry, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuoh-ku, Chiba 260-8717, JapanSearch for more papers by this author First published: 10 January 2001 https://doi.org/10.1002/1096-911X(20010101)36:1 3.0.CO;2-RCitations: 15AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Background Neuroblastoma (NBL) is one of the most common solid malignancies in childhood and is derived from the sympathetic precursor cells. Although p53, a tumor suppressor, has been reported to be rarely mutated in NBLs, it is sequestered abnormally in the cytoplasm of the NBL cell. The mechanism and functional role of the abnormal intracellular localization of p53 remain unclear. Procedure Here, we established an in vitro system of apoptosis model using a NBL cell line CHP134 which also showed a cytoplasmic sequestration of p53. The treatment of the cells with 1 or 5 μM all-trans retinoic acid (RA) induced moderate neurite outgrowth followed by massive death of CHP134 cells by days 5 to 6. Results TUNEL staining showed that the cell death was due to apoptosis. Immunofluorescent stain demonstrated that p53 was strongly positive in the nucleus on day 5, which was accompanied with induction of p21WAF1. In addition, expression of caspase-3 was also increased during the cell death. Intriguingly, the RA treatment induced expression of Ret tyrosine kinase receptor in CHP134 cells. Conclusions The addition of ligands, glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN), inhibited apoptosis as well as nuclear accumulation of p53 in the cell. The present results suggest that the RA-induced apoptosis of NBL cells is associated with activation of both the caspase cascade and the p53-mediated pathway with its nuclear translocation. The neurotrophic signal through the GDNF-Ret system may prevent the neuronal cell death. Med. Pediatr. Oncol. 36:122–126, 2001. © 2001 Wiley-Liss, Inc. Citing Literature Volume36, Issue1Special Issue: Advances in Neuroblastoma Research: 1998 Conference1 January 2001Pages 122-126 RelatedInformation