| Loss of pRB and p107 disrupts cartilage development and promotes enchondroma formation. | |
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MedLine Citation:
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PMID: 23146901 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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.Oncogene advance online publication, 12 November 2012; doi:10.1038/onc.2012.496. |
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Authors:
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A S Landman; P S Danielian; J A Lees |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-11-12 |
Journal Detail:
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Title: Oncogene Volume: - ISSN: 1476-5594 ISO Abbreviation: Oncogene Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8711562 Medline TA: Oncogene Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA. |
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