We are upgrading the repository! A content freeze is in effect until December 6, 2024. New submissions or changes to existing items will not be allowed during this period. All content already published will remain publicly available for searching and downloading. Updates will be posted in the Website Upgrade 2024 FAQ in the sidebar Help menu. Reach out to escholarship@umassmed.edu with any questions.
Impaired cell cycle regulation of the osteoblast-related heterodimeric transcription factor Runx2-Cbfbeta in osteosarcoma cells
Authors
San Martin, Inga A.Varela, Nelson
Gaete, Marcia
Villegas, Karina
Osorio, Mariana
Tapia, Julio
Antonelli, Marcelo
Mancilla, Edna E.
Pereira, Barry P.
Nathan, Saminathan S.
Lian, Jane B.
Stein, Janet L.
Stein, Gary S.
Van Wijnen, Andre J.
Galindo, Mario
UMass Chan Affiliations
Department of Cell BiologyDocument Type
Journal ArticlePublication Date
2009-12-10Keywords
AnimalsCell Cycle
Cell Line
Cell Line, Tumor
Core Binding Factor Alpha 1 Subunit
Core Binding Factor beta Subunit
Cysteine Proteinase Inhibitors
G1 Phase
Gene Expression
Gene Expression Regulation, Neoplastic
Humans
Leupeptins
Mice
Mitosis
Osteoblasts
Osteosarcoma
Proteasome Endopeptidase Complex
Rats
Ubiquitination
Cell Biology
Metadata
Show full item recordAbstract
Bone formation and osteoblast differentiation require the functional expression of the Runx2/Cbfbeta heterodimeric transcription factor complex. Runx2 is also a suppressor of proliferation in osteoblasts by attenuating cell cycle progression in G(1). Runx2 levels are modulated during the cell cycle, which are maximal in G(1) and minimal beyond the G(1)/S phase transition (S, G(2), and M phases). It is not known whether Cbfbeta gene expression is cell cycle controlled in preosteoblasts nor how Runx2 or Cbfbeta are regulated during the cell cycle in bone cancer cells. We investigated Runx2 and Cbfbeta gene expression during cell cycle progression in MC3T3-E1 osteoblasts, as well as ROS17/2.8 and SaOS-2 osteosarcoma cells. Runx2 protein levels are reduced as expected in MC3T3-E1 cells arrested in late G(1) (by mimosine) or M phase (by nocodazole), but not in cell cycle arrested osteosarcoma cells. Cbfbeta protein levels are cell cycle independent in both osteoblasts and osteosarcoma cells. In synchronized MC3T3-E1 osteoblasts progressing from late G1 or mitosis, Runx2 levels but not Cbfbeta levels are cell cycle regulated. However, both factors are constitutively elevated throughout the cell cycle in osteosarcoma cells. Proteasome inhibition by MG132 stabilizes Runx2 protein levels in late G(1) and S in MC3T3-E1 cells, but not in ROS17/2.8 and SaOS-2 osteosarcoma cells. Thus, proteasomal degradation of Runx2 is deregulated in osteosarcoma cells. We propose that cell cycle control of Runx2 gene expression is impaired in osteosarcomas and that this deregulation may contribute to the pathogenesis of osteosarcoma.Source
J Cell Physiol. 2009 Dec;221(3):560-71. Link to article on publisher's siteDOI
10.1002/jcp.21894Permanent Link to this Item
http://hdl.handle.net/20.500.14038/49599PubMed ID
19739101Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1002/jcp.21894