Loss of a FYN-regulated differentiation and growth arrest pathway in advanced stage neuroblastoma

被引：108

作者：

Berwanger, B

Hartmann, O

Bergmann, E

Bernard, S

Nielsen, D

Krause, M

Kartal, A

Flynn, D

Wiedemeyer, R

Schwab, M

Schäfer, H

Christiansen, H

Eilers, M

机构：

[1] Inst Mol Biol & Tumor Res IMT, D-35037 Marburg, Germany

[2] Inst Med Biometry & Epidemiol, D-35037 Marburg, Germany

[3] Childrens Hosp, D-35037 Marburg, Germany

[4] W Virginia Univ, Mary Babb Randolph Canc Ctr, Morgantown, WV 26506 USA

[5] W Virginia Univ, Dept Microbiol Immunol & Cell Biol, Morgantown, WV 26506 USA

[6] German Canc Res Ctr, Dept Cytogenet H0400, D-69120 Heidelberg, Germany

来源：

CANCER CELL | 2002年 / 2卷 / 05期

关键词：

D O I：

10.1016/S1535-6108(02)00179-4

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Tumor stage, age of patient, and amplification of MYCN predict disease outcome in neuroblastoma. To gain insight into the underlying molecular pathways, we have obtained expression profiles from 94 primary neuroblastoma specimens. Advanced tumor stages show a characteristic expression profile that includes downregulation of multiple genes involved in signal transduction through Fyn and the actin cytoskeleton. High expression of Fyn and high Fyn kinase activity are restricted to low-stage tumors. In culture, expression of active Fyn kinase induces differentiation and growth arrest of neuroblastoma cells. Expression of Fyn predicts long-term survival independently of MYCN amplification. Amplification of MYCN correlates with deregulation of a distinct set of genes, many of which are target genes of Myc. Our data demonstrate a causal role for Fyn kinase in the genesis of neuroblastoma.

引用

页码：377 / 386

页数：10

共 47 条

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