Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

Loss of cyclin D1 impairs cerebellar development and suppresses medulloblastoma formation.

Authors: Pogoriler, Jennifer  Millen, Kathleen  Utset, Manuel  Du, Wei 
Citation: Pogoriler J, etal., Development. 2006 Oct;133(19):3929-37. doi: 10.1242/dev.02556. Epub 2006 Aug 30.
Pubmed: (View Article at PubMed) PMID:16943274
DOI: Full-text: DOI:10.1242/dev.02556

Medulloblastoma, the most common malignant brain tumor of childhood, is believed to derive from immature granule neuron precursors (GNPs) that normally proliferate in the external granule layer before exiting the cell cycle and migrating to their mature location in the inner granule layer. In this study, we examined the expression of D type cyclins in GNPs during cerebellar development and showed that GNPs in early development expressed only cyclin D1, whereas later GNPs expressed both cyclins D1 and D2. Coinciding with the period of cyclin D1-only expression, Ccnd1(-/-) mice showed reduced proliferation of GNPs and impaired growth of the cerebellum. Interestingly, removal of cyclin D1 was sufficient to drastically reduce the incidence of medulloblastoma in Ptch1(+/-) mice, despite the fact that these tumors showed upregulation of both cyclins D1 and D2. We showed that cyclin D1 has an earlier role in tumorigenesis: in the absence of cyclin D1, the incidence and overall volume of ;preneoplastic' lesions were significantly decreased. We propose a model that links a role of cyclin D1 in normal GNP proliferation with its early role in tumorigenesis.

Annotation

Disease Annotations
Objects Annotated

Additional Information

 
CRRD Object Information
CRRD ID: 13681932
Created: 2018-07-12
Species: All species
Last Modified: 2018-07-12
Status: ACTIVE



NHLBI Logo

RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.