| First Author | Hatton BA | Year | 2006 |
| Journal | Cancer Res | Volume | 66 |
| Issue | 17 | Pages | 8655-61 |
| PubMed ID | 16951180 | Mgi Jnum | J:112411 |
| Mgi Id | MGI:3656309 | Doi | 10.1158/0008-5472.CAN-06-1621 |
| Citation | Hatton BA, et al. (2006) N-myc Is an Essential Downstream Effector of Shh Signaling during both Normal and Neoplastic Cerebellar Growth. Cancer Res 66(17):8655-61 |
| abstractText | 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-myc(Fl/Fl) and c-myc(Fl/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). |
