Distinct Neural Stem Cell Populations Give Rise to Disparate Brain Tumors in Response to N-MYC

被引：169

作者：

Swartling, Fredrik J. ^{[1
,2
,3
,4
,5
,6
]}

Savov, Vasil ^{[6
]}

Persson, Anders I. ^{[1
,2
,3
,4
,5
]}

Chen, Justin ^{[1
,2
,3
,4
,5
]}

Hackett, Christopher S. ^{[1
,2
,3
,4
,5
]}

Northcott, Paul A. ^{[7
]}

Grimmer, Matthew R. ^{[1
,2
,3
,4
,5
]}

Lau, Jasmine ^{[1
,2
,3
,4
,5
]}

Chesler, Louis ^{[8
]}

Perry, Arie ^{[1
,2
,3
,4
,5
]}

Phillips, Joanna J. ^{[1
,2
,3
,4
,5
]}

Taylor, Michael D. ^{[7
]}

Weiss, William A. ^{[1
,2
,3
,4
,5
]}

机构：

[1] Univ Calif San Francisco, Brain Tumor Res Ctr, Dept Neurol, San Francisco, CA 94158 USA

[2] Univ Calif San Francisco, Brain Tumor Res Ctr, Dept Pathol, San Francisco, CA 94158 USA

[3] Univ Calif San Francisco, Brain Tumor Res Ctr, Dept Pediat, San Francisco, CA 94158 USA

[4] Univ Calif San Francisco, Brain Tumor Res Ctr, Dept Neurosurg, San Francisco, CA 94158 USA

[5] Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA

[6] Uppsala Univ, Rudbeck Lab, Dept Immunol Genet & Pathol, SE-75185 Uppsala, Sweden

[7] Hosp Sick Children, Toronto, ON M5G 1X8, Canada

[8] Inst Canc Res, Sutton SM2 5NG, Surrey, England

来源：

CANCER CELL | 2012年 / 21卷 / 05期

基金：

瑞典研究理事会;

关键词：

SONIC HEDGEHOG; MOUSE MODEL; PEDIATRIC MEDULLOBLASTOMA; EMBRYONIC LETHALITY; SOX9; EXPRESSION; MUTATIONS; PROLIFERATION; PROGENITORS; GENERATION; ASTROCYTES;

D O I：

10.1016/j.ccr.2012.04.012

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The proto-oncogene MYCN is mis-expressed in various types of human brain tumors. To clarify how developmental and regional differences influence transformation, we transduced wild-type or mutationally stabilized murine N-myc(T58A) into neural stem cells (NSCs) from perinatal murine cerebellum, brain stem, and forebrain. Transplantation of N-myc(WT) NSCs was insufficient for tumor formation. N-myc(T58A) cerebellar and brain stem NSCs generated medulloblastoma/primitive neuroectodermal tumors, whereas forebrain NSCs developed diffuse glioma. Expression analyses distinguished tumors generated from these different regions, with tumors from embryonic versus postnatal cerebellar NSCs demonstrating Sonic Hedgehog (SHH) dependence and SHH independence, respectively. These differences were regulated in part by the transcription factor SOX9, activated in the SHH subclass of human medulloblastoma. Our results demonstrate context-dependent transformation of NSCs in response to a common oncogenic signal.

引用

页码：601 / 613

页数：13

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