Induction of medulloblastomas in mice by sonic hedgehog, independent of Gli1.

Abstract:

:The Sonic hedgehog (Shh) signaling pathway plays a critical role in normal cerebellar development and has been implicated in medulloblastomas, common malignant childhood tumors of the cerebellum. To test whether Shh mis-expression is sufficient for medulloblastoma formation, we used ultrasound biomicroscopy-guided in utero injection of a Shh-expressing retrovirus into the cerebellum of 13.5-day mouse embryos to show that direct activation of the Shh pathway can lead to tumor formation. Significantly, medulloblastomas were observed in 76% of the mice infected with Shh-expressing retrovirus. Furthermore, contrary to recent suggestions that the Shh transcriptional target Gli1 plays a critical role in Shh-induced tumorigenesis, we found that medulloblastomas form in Gli1 null mutant mice. We have developed an efficient mouse model of medulloblastoma and shown that Gli1 is not required for tumorigenesis when Shh signaling is activated upstream in the pathway.

journal_name

Cancer Res

journal_title

Cancer research

authors

Weiner HL,Bakst R,Hurlbert MS,Ruggiero J,Ahn E,Lee WS,Stephen D,Zagzag D,Joyner AL,Turnbull DH

subject

Has Abstract

pub_date

2002-11-15 00:00:00

pages

6385-9

issue

22

eissn

0008-5472

issn

1538-7445

journal_volume

62

pub_type

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