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The effects of the insulin-like growth factors and transforming growth factor β on the jun proto-oncogene family in MC3T3-E1 cells

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Abstract

Previous studies have demonstrated that when cells of the mouse osteoblastic cell line MC3T3-E1 are exposed to IGF-I and IGF-II they exhibit rapid and transient induction of the transcript from the proto-oncogene c-fos [8]. To clarify the relationship between induction of cell proliferation and proto-oncogene expression in MC3T3-E1 cells, the acute affects of IGF-I and IGF-II, growth factors that stimulate cell proliferation, and of TGF-β1, which inhibits cell proliferation, northern analyses with cDNA-derived probes for the proto-oncogenes c-jun, jun-B, and jun-D were undertaken. Concurrent northern analyses with a probe for c-fos extended our previous results to include the effect of TGF-β1 on c-fos. IGF-I does not induce the c-jun, jun-B, or jun-D transcripts, the former and latter being produced at detectable levels constitutively. After 1 hour of exposure to IGF-II the c-jun transcript response ranges from onefold to 13-fold and the jun-D transcript response ranges around twofold. After 1 hour of exposure to TGF-β1, the jun-B transcript response ranges from eightfold to 24-fold, the c-fos transcript response ranges between sixfold and sevenfold. The differences observed in the magnitude and kinetics of the induction provoked by these growth factors is consistent with the presence of a regulatory circuit acting through the Jun family members which may act to stimulate transcription differentially when bound to DNA either as homodimers or, with Fos family proteins, as heterodimers.

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References

  1. Ransone LJ, Verma IM (1989) Association of nuclear oncoproteins Fos and Jun. Cur Opin Cell Biol 1:536–540

    Google Scholar 

  2. Gutman A, Wasylyk B (1991) Nuclear targets for transcription regulation by oncogenes. Trends Gene 7:49–54

    Google Scholar 

  3. Riabowol K, Schiff J, Gilman MZ (1992) Transcription factor AP-1 activity is required for initiation of DNA synthesis and is lost during cellular aging. Proc Natl Acad Sci USA 89:157–161

    Google Scholar 

  4. Kovary K, Bravo R (1992) Existence of different Fos/Jun complexes during the G0-to-G1 transition and during exponential growth in mouse fibroblasts: differential role of Fos proteins. Mol Cell Biol 12:5015–5023

    Google Scholar 

  5. Shemshedini L, Knauthe R, Saaone-Corsi P, Pornon A, Gronemeyer H (1991) Cell-specific inhibitory and stimulatory effects of Fos and Jun on transcription activation by nuclear receptors. EMBO 10:3839–3849

    Google Scholar 

  6. Wang Z-Q, Ovitt C, Grigoriadis AE, Mohle-Steinlein U, Ruther U, Wagner EF (1992) Bone and haematopoietic defects in mice lacking c-fos. Nature 360:741–745

    Google Scholar 

  7. Smeyne RJ, Venrell M, Haywood M, Baker SJ, Miao GG, Schilling K, Robertson LM, Curran T, Morgan JI (1993) Continuous c-fos expression precedes programmed cell death in vivo. Nature 363:166–169

    Google Scholar 

  8. Merriman HL, LaTour DA, Linkhart TA, Mohan S, Baylink DJ, Strong DD (1990) Insulin-like growth factor-I and insulinlike growth factor-II induce c-fos in mouse osteoblastic cells. Calcif Tissue Int 46:258–262

    Google Scholar 

  9. Candeliere GA, Prud'homme J, St-Arnaud R (1991) Differential stimulation of Fos and Jun family members by calcitriol in osteoblastic cells. Mol Endocrinol 5:1780–1788

    Google Scholar 

  10. Okazaki R, Ikeda K, Sakamoto A, Nakano T, Morimoto K, Kikuchi T, Urakawa K, Ogata E, Matsumoto T (1992) Transcriptional activation of c-fos and c-jun protooncogenes by serum growth factors in osteoblast-like MC3T3-E1 cells. J Bone Miner Res 7:1149–1155

    Google Scholar 

  11. Amarnani S, Merriman HL, Linkhart TA, Baylink DJ, Mohan S (1993) Autocrine regulators of MC3T3-E1 cell proliferation. J Bone Miner Res 8:157–165

    Google Scholar 

  12. Mohan S, Baylink DJ (1991) Bone growth factors. Clin Orthop 263:30–48

    Google Scholar 

  13. Mohan S, Jennings JJ, Linkhart TA, Baylink DJ (1988) Primary structure of human skeletal growth factor: homology with human insulin-like growth factor-II. Biochim Biophys Acta 966: 44–55

    Google Scholar 

  14. Ausubel FM, Brent R, Kingston RE, Moore DD, Seidman JG, Smith JA, Struhl K (1989) Current protocols in molecular biology. John Wiley & Sons, London, New York

    Google Scholar 

  15. Feinberg AP, Vogelstein B (1983) A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 132:6–13

    Google Scholar 

  16. Lamph WW, Wamsley P, Sassone-Corsi P, Verma IM (1988) Induction of proto-oncogene Jun/AP1 by serum and TPA. Nature 334:629–631

    Google Scholar 

  17. Harpold MM, Evans RM, Salditt-Georgieff M, Darnell JE (1979) Production of mRNA in Chinese hamster cells: relationship of the rate of synthesis to the cytoplasmic concentration of nine specific mRNA sequences. Cell 17:1025–1035

    Google Scholar 

  18. Kasperk CH, Wergedal JE, Mohan S, Long DL, Lau KHW, Baylink DJ (1990) Interactions of growth factors present in bone matrix with bone cells: effects on DNA synthesis and alkaline phosphatase. Growth Factors 3:147–158

    Google Scholar 

  19. Mohan S, Linkhart TA, Rosenfeld R, Baylink DJ (1989) Characterization of the receptor for insulin-like growth factor II in bone cells. J Cell Physiol 140:169–176

    Google Scholar 

  20. Elford PR, Guenther HL, Felix R, Cecchini MG, Fleisch (1987) Transforming growth factor β reduces the phenotypic expression of osteoblastic MC3T3-E1 cells in monolayer culture. Bone 8:259–262

    Google Scholar 

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Strong, D.D., Merriman, H.L., Landale, E.C. et al. The effects of the insulin-like growth factors and transforming growth factor β on the jun proto-oncogene family in MC3T3-E1 cells. Calcif Tissue Int 55, 311–315 (1994). https://doi.org/10.1007/BF00310411

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  • DOI: https://doi.org/10.1007/BF00310411

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