In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 66, No. 17 ( 2006-09-01), p. 8655-8661
Abstract:
We examined the genetic requirements for the Myc family of oncogenes in normal Sonic hedgehog (Shh)–mediated cerebellar granule neuronal precursor (GNP) expansion and in Shh pathway–induced medulloblastoma formation. In GNP-enriched cultures derived from N-mycFl/Fl and c-mycFl/Fl mice, disruption of N-myc, but not c-myc, inhibited the proliferative response to Shh. Conditional deletion of c-myc revealed that, although it is necessary for the general regulation of brain growth, it is less important for cerebellar development and GNP expansion than N-myc. In vivo analysis of compound mutants carrying the conditional N-myc null and the activated Smoothened (ND2:SmoA1) alleles showed, that although granule cells expressing the ND2:SmoA1 transgene are present in the N-myc null cerebellum, no hyperproliferation or tumor formation was detected. Taken together, these findings provide in vivo evidence that N-myc acts downstream of Shh/Smo signaling during GNP proliferation and that N-myc is required for medulloblastoma genesis even in the presence of constitutively active signaling from the Shh pathway. (Cancer Res 2006; 66(17): 8655-61)
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/0008-5472.CAN-06-1621
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2006
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2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3