Accelerated cell cycle progression in osteoblasts overexpressing the c-fos proto-oncogene: induction of cyclin A and enhanced CDK2 activity - PubMed (original) (raw)
. 2004 Mar 12;279(11):9882-91.
doi: 10.1074/jbc.M310184200. Epub 2003 Dec 29.
Affiliations
- PMID: 14699150
- DOI: 10.1074/jbc.M310184200
Free article
Accelerated cell cycle progression in osteoblasts overexpressing the c-fos proto-oncogene: induction of cyclin A and enhanced CDK2 activity
Andrew Sunters et al. J Biol Chem. 2004.
Free article
Abstract
Transgenic mice overexpressing the c-Fos oncoprotein develop osteosarcomas that are associated with deregulated expression of cell cycle genes. Here we have generated osteoblast cell lines expressing c-fos under the control of a tetracycline-regulatable promoter to investigate the role of c-Fos in osteoblast cell cycle control in vitro. Three stable subclones, AT9.2, AT9.3, and AT9.7, derived from MC3T3-E1 mouse osteoblasts, expressed high levels of exogenous c-fos mRNA and protein in the absence of tetracycline. Functional contribution of ectopic c-Fos to AP-1 complexes was confirmed by electromobility shift assays and transactivation of AP-1 reporter constructs. Induction of exogenous c-Fos in quiescent AT9.2 cells caused accelerated S-phase entry following serum stimulation, resulting in enhanced growth rate. Ectopic c-Fos resulted in increased expression of cyclins A and E protein levels, and premature activation of cyclin A-, cyclin E-, and cyclin-dependent kinase (CDK) 2-associated kinase activities, although cyclin D levels and CDK4 activity were not affected significantly in these cell lines. The enhanced CDK2 kinase activity was associated with a rapid, concomitant dissociation of p27 from CDK2-containing complexes. Deregulated cyclin A expression and CDK2 activity was also observed in primary mouse osteoblasts overexpressing c-Fos, but not in fibroblasts, and c-Fos transgenic tumor-derived osteosarcoma cells constitutively expressed high levels of cyclin A protein. These data suggest that overexpression of c-Fos in osteoblasts results in accelerated S phase entry as a result of deregulated cyclin A/E-CDK2 activity. This represents a novel role for c-Fos in osteoblast growth control and may provide c-Fos-overexpressing osteoblasts with a growth advantage during tumorigenesis.
Similar articles
- BCL-x(L) and BCL2 delay Myc-induced cell cycle entry through elevation of p27 and inhibition of G1 cyclin-dependent kinases.
Greider C, Chattopadhyay A, Parkhurst C, Yang E. Greider C, et al. Oncogene. 2002 Nov 7;21(51):7765-75. doi: 10.1038/sj.onc.1205928. Oncogene. 2002. PMID: 12420213 - Glucocorticoids inhibit developmental stage-specific osteoblast cell cycle. Dissociation of cyclin A-cyclin-dependent kinase 2 from E2F4-p130 complexes.
Smith E, Redman RA, Logg CR, Coetzee GA, Kasahara N, Frenkel B. Smith E, et al. J Biol Chem. 2000 Jun 30;275(26):19992-20001. doi: 10.1074/jbc.M001758200. J Biol Chem. 2000. PMID: 10867026 - Cell cycle progression without cyclin E/CDK2: breaking down the walls of dogma.
Gladden AB, Diehl JA. Gladden AB, et al. Cancer Cell. 2003 Sep;4(3):160-2. doi: 10.1016/s1535-6108(03)00217-4. Cancer Cell. 2003. PMID: 14522248 Review. - Cyclin E.
Möröy T, Geisen C. Möröy T, et al. Int J Biochem Cell Biol. 2004 Aug;36(8):1424-39. doi: 10.1016/j.biocel.2003.12.005. Int J Biochem Cell Biol. 2004. PMID: 15147722 Review.
Cited by
- c-Fos overexpression increases the proliferation of human hepatocytes by stabilizing nuclear Cyclin D1.
Güller M, Toualbi-Abed K, Legrand A, Michel L, Mauviel A, Bernuau D, Daniel F. Güller M, et al. World J Gastroenterol. 2008 Nov 7;14(41):6339-46. doi: 10.3748/wjg.14.6339. World J Gastroenterol. 2008. PMID: 19009649 Free PMC article. - Fra-1 promotes growth and survival in RAS-transformed thyroid cells by controlling cyclin A transcription.
Casalino L, Bakiri L, Talotta F, Weitzman JB, Fusco A, Yaniv M, Verde P. Casalino L, et al. EMBO J. 2007 Apr 4;26(7):1878-90. doi: 10.1038/sj.emboj.7601617. Epub 2007 Mar 8. EMBO J. 2007. PMID: 17347653 Free PMC article. - Terminal osteoblast differentiation, mediated by runx2 and p27KIP1, is disrupted in osteosarcoma.
Thomas DM, Johnson SA, Sims NA, Trivett MK, Slavin JL, Rubin BP, Waring P, McArthur GA, Walkley CR, Holloway AJ, Diyagama D, Grim JE, Clurman BE, Bowtell DD, Lee JS, Gutierrez GM, Piscopo DM, Carty SA, Hinds PW. Thomas DM, et al. J Cell Biol. 2004 Dec 6;167(5):925-34. doi: 10.1083/jcb.200409187. J Cell Biol. 2004. PMID: 15583032 Free PMC article. - Expression of thioredoxin during progression of hamster and human cholangiocarcinoma.
Yoon BI, Kim YH, Yi JY, Kang MS, Jang JJ, Joo KH, Kim Y, McHugh Law J, Kim DY. Yoon BI, et al. Cancer Sci. 2010 Jan;101(1):281-8. doi: 10.1111/j.1349-7006.2009.01353.x. Epub 2009 Sep 8. Cancer Sci. 2010. PMID: 19799607 Free PMC article. - NFATc1 targets cyclin A in the regulation of vascular smooth muscle cell multiplication during restenosis.
Karpurapu M, Wang D, Singh NK, Li Q, Rao GN. Karpurapu M, et al. J Biol Chem. 2008 Sep 26;283(39):26577-90. doi: 10.1074/jbc.M800423200. Epub 2008 Jul 29. J Biol Chem. 2008. PMID: 18667424 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources