An integrated approach identifies Nhlh1 and Insm1 as Sonic Hedgehog-regulated genes in developing cerebellum and medulloblastoma

被引：51

作者：

De Smaele, Enrico ^{[1
]}

Fragomeli, Caterina ^{[1
]}

Ferretti, Elisabetta ^{[1
]}

Pelloni, Marianna ^{[1
]}

Po, Agnese ^{[1
]}

Canettieri, Gianluca ^{[1
]}

Coni, Sonia ^{[1
]}

Di Marcotullio, Lucia ^{[1
]}

Greco, Azzura ^{[1
]}

Moretti, Marta ^{[1
]}

Di Rocco, Concezio ^{[2
]}

Pazzaglia, Simona ^{[3
]}

Maroder, Marella ^{[1
]}

Screpanti, Isabella ^{[1
]}

Giannini, Giuseppe ^{[1
]}

Gulino, Alberto ^{[1
,4
]}

机构：

[1] Univ Roma La Sapienza, Dept Expt Med, I-00161 Rome, Italy

[2] Catholic Univ, Neurosurg Inst, Rome, Italy

[3] Ente Nuove Technol Energia & Ambiente, Biotechnol Unit, Ctr Ricerche Casaccia, Rome, Italy

[4] Neuromed Inst, Pozzilli, Isernia, Italy

来源：

NEOPLASIA | 2008年 / 10卷 / 01期

关键词：

D O I：

10.1593/neo.07891

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Medulloblastoma (MB) is the most common malignant brain tumor of childhood arising from deregulated cerebellar development. Sonic Hedgehog (Shh) pathway plays a critical role in cerebellar development and its aberrant expression has been identified in MB. Gene expression profiling of cerebella from 1- to 14-day-old mice unveiled a cluster of genes whose expression correlates with the levels of Hedgehog (HH) activity. From this cluster, we identified Insm1 and Nhlh1/NSCL1 as novel HH targets induced by Shh treatment in cultured cerebellar granule cell progenitors. Nhlh1 promoter was found to be bound and activated by Gli1 transcription factor. Remarkably, the expression of these genes is also upregulated in mouse and human HH-dependent MBs, suggesting that they may be either a part of the HH-induced tumorigenic process or a specific trait of HH-dependent tumor cells.

引用

页码：89 / 98

页数：10

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