Document Detail


Loss of pRB and p107 disrupts cartilage development and promotes enchondroma formation.
MedLine Citation:
PMID:  23146901     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The pocket proteins pRB, p107 and p130 have established roles in regulating the cell cycle through the control of E2F activity. The pocket proteins regulate differentiation of a number of tissues in both cell cycle-dependent and -independent manners. Prior studies showed that mutation of p107 and p130 in the mouse leads to defects in cartilage development during endochondral ossification, the process by which long bones form. Despite evidence of a role for pRB in osteoblast differentiation, it is unknown whether it functions during cartilage development. Here, we show that mutation of Rb in the early mesenchyme of p107-mutant mice results in severe cartilage defects in the growth plates of long bones. This is attributable to inappropriate chondrocyte proliferation that persists after birth and leads to the formation of enchondromas in the growth plates as early as 8 weeks of age. Genetic crosses show that development of these tumorigenic lesions is E2f3 dependent. These results reveal an overlapping role for pRB and p107 in cartilage development, endochondral ossification and enchondroma formation that reflects their coordination of cell-cycle exit at appropriate developmental stages.
Authors:
A S Landman; P S Danielian; J A Lees
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-11-12
Journal Detail:
Title:  Oncogene     Volume:  32     ISSN:  1476-5594     ISO Abbreviation:  Oncogene     Publication Date:  2013 Oct 
Date Detail:
Created Date:  2013-10-04     Completed Date:  2013-11-22     Revised Date:  2014-02-25    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  4798-805     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Chondrogenesis / genetics,  physiology*
Chondroma / genetics*,  pathology
Growth Plate / growth & development*
Mice
Mice, Knockout
Mutation
Real-Time Polymerase Chain Reaction
Retinoblastoma Protein / genetics,  physiology*
Retinoblastoma-Like Protein p107 / genetics,  physiology*
Tomography, X-Ray Computed
Grant Support
ID/Acronym/Agency:
CA121921/CA/NCI NIH HHS; R01 CA121921/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Rbl1 protein, mouse; 0/Retinoblastoma Protein; 0/Retinoblastoma-Like Protein p107
Comments/Corrections

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