이정수 (Dana-Farber Cancer Institute, 현 생명공학연구원) | 한빛사논문 > 한빛사

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Dana-Farber Cancer Institute, 현 생명공학연구원

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Cancer Cell, Volume 21, Issue 3, 362-373, 20 March 2012 | 10.1016/j.ccr.2012.02.010 Activated ALK Collaborates with MYCN in Neuroblastoma Pathogenesis

Abstract

Shizhen Zhu,^1,6 Jeong-Soo Lee,^1,6,8 Feng Guo,¹ Jimann Shin,^1,9 Antonio R. Perez-Atayde,² Jeffery L. Kutok,^3,10 Scott J. Rodig,³ Donna S. Neuberg,⁴ Daniel Helman,¹ Hui Feng,¹ Rodney A. Stewart,^1,7 Wenchao Wang,¹ Rani E. George,^1,5 John P. Kanki,¹ and A. Thomas Look^1,5,*

¹Department of Pediatric Oncology, Dana-Farber Cancer Institute
²Department of Pathology, Children’s Hospital Boston
³Department of Pathology, Brigham and Women’s Hospital
⁴Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute
⁵Division of Hematology/Oncology, Children’s Hospital Boston
Harvard Medical School, Boston, MA 02115, USA
⁶These authors contributed equally to this work
⁷Present address: Huntsman Cancer Institute, Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112, USA
⁸Present address: Korea Research Institute of Bioscience and Biotechnology, Aging Research Center, Daejeon 305-806, Korea
⁹Present address: Department of Developmental Biology, Washington University School of Medicine, Saint Louis, MO 63110, USA
¹⁰Present address: Molecular Pathology, Infinity Pharmaceuticals, Cambridge, MA 02139, USA

*Correspondence: A. Thomas Look

Summary
Amplification of the MYCN oncogene in childhood neuroblastoma is often accompanied by mutational activation of ALK (anaplastic lymphoma kinase), suggesting their pathogenic cooperation. We generated a transgenic zebrafish model of neuroblastoma in which MYCN-induced tumors arise from a subpopulation of neuroblasts that migrate into the adrenal medulla analog following organogenesis. Coexpression of activated ALK with MYCN in this model triples the disease penetrance and markedly accelerates tumor onset. MYCN overexpression induces adrenal sympathetic neuroblast hyperplasia, blocks chromaffin cell differentiation, and ultimately triggers a developmentally-timed apoptotic response in the hyperplastic sympathoadrenal cells. Coexpression of activated ALK with MYCN provides prosurvival signals that block this apoptotic response and allow continued expansion and oncogenic transformation of hyperplastic neuroblasts, thus promoting progression to neuroblastoma.

논문정보

형식Research article
게재일2012년 03월 (BRIC 등록일 )
연구진국외 연구진
분야 생명과학 > 감염생물학
피인용횟수120회 이상 인용된 논문 (상위피인용논문 등록일 2018-07-16)

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