Osteoblasts are target cells for transformation in c-fos transgenic mice

doi:10.1083/jcb.122.3.685

This Article

	Full Text (PDF, 8143K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JCB
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Grigoriadis, A. E.
	Articles by Wagner, E. F.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Grigoriadis, A. E.
	Articles by Wagner, E. F.


Social Bookmarking

	What's this?

ARTICLES

Osteoblasts are target cells for transformation in c-fos transgenic mice

AE Grigoriadis, K Schellander, ZQ Wang and EF Wagner
Research Institute of Molecular Pathology, Vienna, Austria.

We have generated transgenic mice expressing the proto-oncogene c-fos from an H-2Kb class I MHC promoter as a tool to identify and isolate cell populations which are sensitive to altered levels of Fos protein. All homozygous H2-c-fosLTR mice develop osteosarcomas with a short latency period. This phenotype is specific for c-fos as transgenic mice expressing the fos- and jun-related genes, fosB and c-jun, from the same regulatory elements do not develop any pathology despite high expression in bone tissues. The c-fos transgene is not expressed during embryogenesis but is expressed after birth in bone tissues before the onset of tumor formation, specifically in putative preosteoblasts, bone- forming osteoblasts, osteocytes, as well as in osteoblastic cells present within the tumors. Primary and clonal cell lines established from c-fos-induced tumors expressed high levels of exogenous c-fos as well as the bone cell marker genes, type I collagen, alkaline phosphatase, and osteopontin/2ar. In contrast, osteocalcin/BGP expression was either low or absent. All cell lines were tumorigenic in vivo, some of which gave rise to osteosarcomas, expressing exogenous c- fos mRNA, and Fos protein in osteoblastic cells. Detailed analysis of one osteogenic cell line, P1, and several P1-derived clonal cell lines indicated that bone-forming osteoblastic cells were transformed by Fos. The regulation of osteocalcin/BGP and alkaline phosphatase gene expression by 1,25-dihydroxyvitamin D3 was abrogated in P1-derived clonal cells, whereas glucocorticoid responsiveness was unaltered. These results suggest that high levels of Fos perturb the normal growth control of osteoblastic cells and exert specific effects on the expression of the osteoblast phenotype.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Rangaswami, H., Marathe, N., Zhuang, S., Chen, Y., Yeh, J.-C., Frangos, J. A., Boss, G. R., Pilz, R. B. (2009). Type II cGMP-dependent Protein Kinase Mediates Osteoblast Mechanotransduction. J. Biol. Chem. 284: 14796-14808 [Abstract] [Full Text]
Leaner, V. D., Chick, J. F., Donninger, H., Linniola, I., Mendoza, A., Khanna, C., Birrer, M. J. (2009). Inhibition of AP-1 Transcriptional Activity Blocks the Migration, Invasion, and Experimental Metastasis of Murine Osteosarcoma. Am. J. Pathol. 174: 265-275 [Abstract] [Full Text]
Durchdewald, M., Guinea-Viniegra, J., Haag, D., Riehl, A., Lichter, P., Hahn, M., Wagner, E. F., Angel, P., Hess, J. (2008). Podoplanin Is a Novel Fos Target Gene in Skin Carcinogenesis. Cancer Res. 68: 6877-6883 [Abstract] [Full Text]
Fauquier, L., Duboe, C., Jore, C., Trouche, D., Vandel, L. (2008). Dual role of the arginine methyltransferase CARM1 in the regulation of c-Fos target genes. FASEB J. 22: 3337-3347 [Abstract] [Full Text]
Eferl, R., Hasselblatt, P., Rath, M., Popper, H., Zenz, R., Komnenovic, V., Idarraga, M.-H., Kenner, L., Wagner, E. F. (2008). Development of pulmonary fibrosis through a pathway involving the transcription factor Fra-2/AP-1. Proc. Natl. Acad. Sci. USA 105: 10525-10530 [Abstract] [Full Text]
Walkley, C. R., Qudsi, R., Sankaran, V. G., Perry, J. A., Gostissa, M., Roth, S. I., Rodda, S. J., Snay, E., Dunning, P., Fahey, F. H., Alt, F. W., McMahon, A. P., Orkin, S. H. (2008). Conditional mouse osteosarcoma, dependent on p53 loss and potentiated by loss of Rb, mimics the human disease. Genes Dev. 22: 1662-1676 [Abstract] [Full Text]
Adiseshaiah, P., Lindner, D. J., Kalvakolanu, D. V., Reddy, S. P. (2007). FRA-1 Proto-Oncogene Induces Lung Epithelial Cell Invasion and Anchorage-Independent Growth In vitro, but Is Insufficient to Promote Tumor Growth In vivo. Cancer Res. 67: 6204-6211 [Abstract] [Full Text]
Karsenty, G. (2007). Update on the Transcriptional Control of Osteoblast Differentiation. IBMS BoneKEy 4: 164-170 [Abstract] [Full Text]
Hyun, J., Becam, I., Yanicostas, C., Bohmann, D. (2006). Control of G2/M Transition by Drosophila Fos. Mol. Cell. Biol. 26: 8293-8302 [Abstract] [Full Text]
Xu, Z., Choudhary, S., Voznesensky, O., Mehrotra, M., Woodard, M., Hansen, M., Herschman, H., Pilbeam, C. (2006). Overexpression of Cox-2 in Human Osteosarcoma Cells Decreases Proliferation and Increases Apoptosis.. Cancer Res. 66: 6657-6664 [Abstract] [Full Text]
Ijiri, K., Zerbini, L. F., Peng, H., Correa, R. G., Lu, B., Walsh, N., Zhao, Y., Taniguchi, N., Huang, X.-L., Otu, H., Wang, H., Wang, J. F., Komiya, S., Ducy, P., Rahman, M. U., Flavell, R. A., Gravallese, E. M., Oettgen, P., Libermann, T. A., Goldring, M. B. (2005). A Novel Role for GADD45{beta} as a Mediator of MMP-13 Gene Expression during Chondrocyte Terminal Differentiation. J. Biol. Chem. 280: 38544-38555 [Abstract] [Full Text]
Hwang, S.-G., Yu, S.-S., Poo, H., Chun, J.-S. (2005). c-Jun/Activator Protein-1 Mediates Interleukin-1{beta}-induced Dedifferentiation but Not Cyclooxygenase-2 Expression in Articular Chondrocytes. J. Biol. Chem. 280: 29780-29787 [Abstract] [Full Text]
Harrison, J. R., Huang, Y.-F., Wilson, K. A., Kelly, P. L., Adams, D. J., Gronowicz, G. A., Clark, S. H. (2005). Col1a1 Promoter-targeted Expression of p20 CCAAT Enhancer-binding Protein {beta} (C/EBP{beta}), a Truncated C/EBP{beta} Isoform, Causes Osteopenia in Transgenic Mice. J. Biol. Chem. 280: 8117-8124 [Abstract] [Full Text]
Zayzafoon, M., Fulzele, K., McDonald, J. M. (2005). Calmodulin and Calmodulin-dependent Kinase II{alpha} Regulate Osteoblast Differentiation by Controlling c-fos Expression. J. Biol. Chem. 280: 7049-7059 [Abstract] [Full Text]
Naito, J., Kaji, H., Sowa, H., Hendy, G. N., Sugimoto, T., Chihara, K. (2005). Menin Suppresses Osteoblast Differentiation by Antagonizing the AP-1 Factor, JunD. J. Biol. Chem. 280: 4785-4791 [Abstract] [Full Text]
Thomas, D. M., Johnson, S. A., Sims, N. A., Trivett, M. K., Slavin, J. L., Rubin, B. P., Waring, P., McArthur, G. A., Walkley, C. R., Holloway, A. J., Diyagama, D., Grim, J. E., Clurman, B. E., Bowtell, D. D.L., Lee, J.-S., Gutierrez, G. M., Piscopo, D. M., Carty, S. A., Hinds, P. W. (2004). Terminal osteoblast differentiation, mediated by runx2 and p27KIP1, is disrupted in osteosarcoma. JCB 167: 925-934 [Abstract] [Full Text]
Inoue, D., Kido, S., Matsumoto, T. (2004). Transcriptional Induction of FosB/{Delta}FosB Gene by Mechanical Stress in Osteoblasts. J. Biol. Chem. 279: 49795-49803 [Abstract] [Full Text]
Narayanan, K., Srinivas, R., Peterson, M. C., Ramachandran, A., Hao, J., Thimmapaya, B., Scherer, P. E., George, A. (2004). Transcriptional Regulation of Dentin Matrix Protein 1 by JunB and p300 during Osteoblast Differentiation. J. Biol. Chem. 279: 44294-44302 [Abstract] [Full Text]
Kveiborg, M., Sabatakos, G., Chiusaroli, R., Wu, M., Philbrick, W. M., Horne, W. C., Baron, R. (2004). {Delta}FosB Induces Osteosclerosis and Decreases Adipogenesis by Two Independent Cell-Autonomous Mechanisms. Mol. Cell. Biol. 24: 2820-2830 [Abstract] [Full Text]
Sunters, A., Thomas, D. P., Yeudall, W. A., Grigoriadis, A. E. (2004). Accelerated Cell Cycle Progression in Osteoblasts Overexpressing the c-fos Proto-oncogene: INDUCTION OF CYCLIN A AND ENHANCED CDK2 ACTIVITY. J. Biol. Chem. 279: 9882-9891 [Abstract] [Full Text]
Kenner, L., Hoebertz, A., Beil, T., Keon, N., Karreth, F., Eferl, R., Scheuch, H., Szremska, A., Amling, M., Schorpp-Kistner, M., Angel, P., Wagner, E. F. (2004). Mice lacking JunB are osteopenic due to cell-autonomous osteoblast and osteoclast defects. JCB 164: 613-623 [Abstract] [Full Text]
Hess, J., Hartenstein, B., Teurich, S., Schmidt, D., Schorpp-Kistner, M., Angel, P. (2003). Defective endochondral ossification in mice with strongly compromised expression of JunB. J. Cell Sci. 116: 4587-4596 [Abstract] [Full Text]
Wagner, E F, Matsuo, K (2003). Signalling in osteoclasts and the role of Fos/AP1 proteins. Ann Rheum Dis 62: ii83-85 [Full Text]
Fu, Q., Jilka, R. L., Manolagas, S. C., O'Brien, C. A. (2002). Parathyroid Hormone Stimulates Receptor Activator of NFkappa B Ligand and Inhibits Osteoprotegerin Expression via Protein Kinase A Activation of cAMP-response Element-binding Protein. J. Biol. Chem. 277: 48868-48875 [Abstract] [Full Text]
Reddy, S. P. M., Mossman, B. T. (2002). Role and regulation of activator protein-1 in toxicant-induced responses of the lung. Am. J. Physiol. Lung Cell. Mol. Physiol. 283: L1161-L1178 [Abstract] [Full Text]
Wagner, E F (2002). Functions of AP1 (Fos/Jun) in bone development. Ann Rheum Dis 61: ii40-42 [Abstract] [Full Text]
Jain, M., Arvanitis, C., Chu, K., Dewey, W., Leonhardt, E., Trinh, M., Sundberg, C. D., Bishop, J. M., Felsher, D. W. (2002). Sustained Loss of a Neoplastic Phenotype by Brief Inactivation of MYC. Science 297: 102-104 [Abstract] [Full Text]
Smith, E., Coetzee, G. A., Frenkel, B. (2002). Glucocorticoids Inhibit Cell Cycle Progression in Differentiating Osteoblasts via Glycogen Synthase Kinase-3beta. J. Biol. Chem. 277: 18191-18197 [Abstract] [Full Text]
Lai, C.-F., Cheng, S.-L. (2002). Signal Transductions Induced by Bone Morphogenetic Protein-2 and Transforming Growth Factor-beta in Normal Human Osteoblastic Cells. J. Biol. Chem. 277: 15514-15522 [Abstract] [Full Text]
Tyson, D. R., Swarthout, J. T., Jefcoat, S. C., Partridge, N. C. (2002). PTH Induction of Transcriptional Activity of the cAMP Response Element-Binding Protein Requires the Serine 129 Site and Glycogen Synthase Kinase-3 Activity, But Not Casein Kinase II Sites. Endocrinology 143: 674-682 [Abstract] [Full Text]
Miyamoto, T., Ohneda, O., Arai, F., Iwamoto, K., Okada, S., Takagi, K., Anderson, D. M., Suda, T. (2001). Bifurcation of osteoclasts and dendritic cells from common progenitors. Blood 98: 2544-2554 [Abstract] [Full Text]
Wong, I. H. N., Chan, A. T., Johnson, P. J. (2000). Quantitative Analysis of Circulating Tumor Cells in Peripheral Blood of Osteosarcoma Patients Using Osteoblast-specific Messenger RNA Markers: A Pilot Study. Clin. Cancer Res. 6: 2183-2188 [Abstract] [Full Text]
Chen, N. X., Ryder, K. D., Pavalko, F. M., Turner, C. H., Burr, D. B., Qiu, J., Duncan, R. L. (2000). Ca2+ regulates fluid shear-induced cytoskeletal reorganization and gene expression in osteoblasts. Am. J. Physiol. Cell Physiol. 278: C989-C997 [Abstract] [Full Text]
Adebanjo, O. A., Biswas, G., Moonga, B. S., Anandatheerthavarada, H. K., Sun, L., Bevis, P. J. R., Sodam, B. R., Lai, F. A., Avadhani, N. G., Zaidi, M. (2000). Novel biochemical and functional insights into nuclear Ca2+ transport through IP3Rs and RyRs in osteoblasts. Am. J. Physiol. Renal Physiol. 278: F784-F791 [Abstract] [Full Text]
Schreiber, M, Wang, Z., Jochum, W, Fetka, I, Elliott, C, Wagner, E. (2000). Placental vascularisation requires the AP-1 component fra1. Development 127: 4937-4948 [Abstract]
Thomas, D., Sunters, A, Gentry, A, Grigoriadis, A. (2000). Inhibition of chondrocyte differentiation in vitro by constitutive and inducible overexpression of the c-fos proto-oncogene. J. Cell Sci. 113: 439-450 [Abstract]
Fitzgerald, J., Dietz, T. J., Hughes-Fulford, M. (2000). Prostaglandin E2-Induced Up-Regulation of c-fos Messenger Ribonucleic Acid Is Primarily Mediated by 3',5'-Cyclic Adenosine Monophosphate in MC3T3-E1 Osteoblasts. Endocrinology 141: 291-298 [Abstract] [Full Text]
Karsenty, G. (1999). The genetic transformation of bone biology. Genes Dev. 13: 3037-3051 [Full Text]
Tyson, D. R., Swarthout, J. T., Partridge, N. C. (1999). Increased Osteoblastic c-fos Expression by Parathyroid Hormone Requires Protein Kinase A Phosphorylation of the Cyclic Adenosine 3',5'-Monophosphate Response Element-Binding Protein at Serine 133. Endocrinology 140: 1255-1261 [Abstract] [Full Text]
FITZGERALD, J., HUGHES-FULFORD, M. (1999). Mechanically induced c-fos expression is mediated by cAMP in MC3T3-E1 osteoblasts. FASEB J. 13: 553-557 [Abstract] [Full Text]
He, H., Qi, X.-M., Grossmann, J., Distelhorst, C. W. (1998). c-Fos Degradation by the Proteasome. AN EARLY, Bcl-2-REGULATED STEP IN APOPTOSIS. J. Biol. Chem. 273: 25015-25019 [Abstract] [Full Text]
Watanabe, H., Saitoh, K., Kameda, T., Murakami, M., Niikura, Y., Okazaki, S., Morishita, Y., Mori, S., Yokouchi, Y., Kuroiwa, A., Iba, H. (1997). Chondrocytes as a specific target of ectopic Fos expression in�early�development. Proc. Natl. Acad. Sci. USA 94: 3994-3999 [Abstract] [Full Text]
Candeliere, G. A., Glorieux, F. H., Prud'homme, J., St.-Arnaud, R. (1995). Increased Expression of the c-fos Proto-Oncogene in Bone from Patients with Fibrous Dysplasia. NEJM 332: 1546-1551 [Abstract] [Full Text]
Grigoriadis, A., Wang, Z., Cecchini, M., Hofstetter, W, Felix, R, Fleisch, H., Wagner, E. (1994). c-Fos: a key regulator of osteoclast-macrophage lineage determination and bone remodeling. Science 266: 443-448 [Abstract]