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Retinoids and a retinoic acid receptor differentially modulate thymosinβ 10 gene expression in transfected neuroblastoma cells

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Summary

  1. 1.

    Investigations have demonstrated that the gene encoding thymosinβ 10 (a 43-amino acid member of a family of related proteins originally described in the rat immune system) is a target for morphogenic retinoids in both human and rat neuroblastoma cells.

  2. 2.

    Structure-activity studies revealed that the stimulatory actions of retinoids upon the thymosinβ 10 gene reflect the differing affinities of retinoid analogues for a retinoic acid receptor.

  3. 3.

    To examine further the possibility that the trophic actions of retinoic acid upon expression of the thymosinβ 10 gene involved retinoid receptors, neuroblastoma cells were transiently transfected with an expression vector encoding the nuclear retinoic acid receptor (α) protein.

  4. 4.

    Northern blot and slot-blot analyses revealed that neuronal cells overexpressing RARα-mRNA exhibited an enhanced sensitivity to exogenous and endogeneous retinoic acid in terms of thymosinβ 10 mRNA. Although the RAR-α gene was expressed (at low levels) a priori in these neuroblastoma cells, retinoic acid (2 × 10−7 M for 3 days) slightly stimulated RAR-α-mRNA accumulation.

  5. 5.

    Collectively, these findings indicate the the retinoic acid receptor (α) is regulated by retinoid acid and that the developmentally regulated, retinoidresponsive thymosinβ 10 gene is a target for this nuclear transcription factor in cells derived from the neural crest.

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References

  • Astrom, A., Pettersson, U., Krust, A., Chambon, P., and Voorhees, J. J. (1991). Retinoic acid and synthetic analogs differentially activate retinoic acid receptor dependent transcription.Biochem. Biophys. Res. Comm. 173339–345.

    Google Scholar 

  • Brand, N. J., Petrovich, M., Krust, A., Chambon, P., De Thé, H., Marchio, A., Tiollais, P., and Dejean, A. (1988). Identification of a second human retinoic acid receptor.Nature (Lond.)322850–853.

    Google Scholar 

  • Cadi, R., Pautou, M.-P., and Dhouailly, D. (1984). Structure-activity relationships of retinoids in the morphogenesis of cutaneous appendages in the chick embryo.J. Invest. Dermatol. 83105–109.

    Google Scholar 

  • Chomczynski, P., and Sacchi, N. (1987). Single-step method of RNA isolation by acid guanidiniumthiocyanate-phenol-chloroform extraction.Anal. Biochem. 162156–159.

    Google Scholar 

  • Condon, M. R., Lyse, T., Seebode, J. J., and Hall, A. K. (1990). Preliminary characterization of the human thymosinβ 10 gene and its expression in the developing human brain.Soc. Neurosci. Abstr. 16(2):663.

    Google Scholar 

  • Durston, A. J., Timmermans, J. P. M., Hage, W. J., Hendriks, H. F. J., de Vries, N. J., Heideveld, M., and Nieuwkoop, P. D. (1989). Retinoic acid causes an anterioposterior transformation in the developing central nervous system.Nature 340140–144.

    Google Scholar 

  • Feinburg, A. P., and Vogelstein, B. (1984). A technique for radiolabelling DNA restriction enodnuclease fragments to high specific activity.Anal. Biochem. 256402–405.

    Google Scholar 

  • Giguere, V., Ong, E. S., Sequi, P., and Evans, R. M. (1987). Identification of a receptor for the morphogen retinoic acid.Nature (Lond.) 330624–629.

    Google Scholar 

  • Green, S., Issemann, I., and Sheer, E. (1988). A versatilein vivo andin vitro expression vector for protein engineering.Nucl. Acid. Res. 16(1):396.

    Google Scholar 

  • Grippo, J. F., and Gudas, L. J. (1987). The effect of dibutyryl cyclic AMP and butyrate on F9 teratocarcinoma cellular retinoic acid-binding protein activity.J. Biol. Chem. 2624492–4500.

    Google Scholar 

  • Hall, A. K. (1991a). Development regulation of thymosin beta-10 mRNA in the human brain.Mol. Brain Res. 9175–177.

    Google Scholar 

  • Hall, A. K. (1991b). Retinoic acid and serum modulation of thymosin beta-10 gene expression in rat neuroblastoma cells.J. Mol. Neurosci. 2229–237.

    Google Scholar 

  • Hall, A. K. (1991c). Differential expression of thymosin genes in human tumors and in the developing human kidney.Int. J. Cancer 48672–677.

    Google Scholar 

  • Hall, A. K., Morgan, J. I., and Seebode, J. J. (1989). Differentiation-associated modulation of thymosin beta-10 expression in neuroblastoma cells by retinoic acid. InAdvances in Gene Technology; Molecular Neurobiology and Neuropharmacology, Vol. 1 Cambridge University Press, Cambridge, p. 70.

    Google Scholar 

  • Hall, A. K., Hempstead, J., and Morgan, J. I. (1990). Retinoic beta-10 levels in developing human brain and its regulation by retinoic acid in the HTB-10 neuroblastoma.Mol. Brain Res. 8129–135.

    Google Scholar 

  • Hall, A. K., Hempstead, J., and Morgan, J. I. (1991a). Retinoic acid regulates thymosin beta-10 levels in rat neuroblastoma cells.J. Neurochem. 56462–468.

    Google Scholar 

  • Hall, A. K., Fernandes, M., and Seebode, J. J. (1991b). Thymosin beta-10: An oncofetal, retinoid-responsive gene expressed in human embryonic tissues and tumors.Miami Short Rep. 177.

    Google Scholar 

  • Hall, A. K., Aten, R., and Behrman, H. R. (1991c). Thymosin gene expression is modulated by pregnant mare's serum gonadotropin, human chorionic gonadotropin and prostaglandin F in the immature rat ovary.Endocrinology 128951–957.

    Google Scholar 

  • Horecker, B. L., and Morgan, J. I. (1984). Ubiquitous distribution of thymosin beta-4 and related peptides in vertebrate cells and tissues.Lymphokines 915–35.

    Google Scholar 

  • Keeble, S., and Maden, M. (1989). The relationship among retinoid structure, affinity for retinoic acid-binding protein, and ability to respecify pattern in the regenerating axolotl limb.Dev. Biol. 13226–34.

    Google Scholar 

  • Leonard, D. G. B., Ziff, E. B., and Greene, L. A. (1987). Identification and characterization of mRNAs regulated by nerve growth factor in PC12 cells.Mol. Cell. Biol. 73156–3167.

    Google Scholar 

  • Leroy, P., Kurst, A., Zelent, A., Mendelsohn, C., Garnier, J.-M., Kastner, P., Dierich, A., and Chambon, P. (1981). Multiple isoforms of the mouse retinoic acid receptor-α induction by retinoic acid.EMBO J. 1059–69.

    Google Scholar 

  • Lin, S.-C., and Morrison-Bogorad, M. (1990). Developmental expression of mRNAs encoding thymosins beta-4 and beta-10 in rat brain and other tissues.J. Mol. Neurosci. 235–44.

    Google Scholar 

  • Lugo, D. L., Chen, S.-C., Hall, A. K., Hempstead, J., Ziai, R., and Morgan, J. I. (1991). Developmental regulation ofβ-thymosins in the rat central nervous system.J. Neurochem. 56456–461.

    Google Scholar 

  • Mangelsdorf, D. J., Ong, E. S., Dyck, J. A., and Evans, R. M. (1990). Nuclear receptor identifies a novel retinoic acid response pathway.Nature 345224–229.

    Google Scholar 

  • Momoi, T., Kitamoto, T., Seno, H., and Momoi, M. (1988). The distribution of cellular retinoic acid binding protein (CRABP) in the central nervous system of the chick embryo during development.Proc. Jpn. Acad. 64294–297.

    Google Scholar 

  • Oro, A. E., McKeown, M., and Evans, R. M. (1990). Relationship between the product of theDrosophila ultraspiracle locus and the vertebrate retinoid X receptor.Nature 347298–301.

    Google Scholar 

  • Petrovich, M., Brand, N. J., Kurst, A., and Chambon, P. A. (1987). A human retinoic acid receptor which belongs to a family of nuclear receptors.Nature 330444–450.

    Google Scholar 

  • Picard, D., Khursheed, B., Garabedian, M. J., Fortin, M. G., Lindquist, S., and Yamamoto, K. R. (1990). Reduced levels of hsp90 compromises steroid receptor actionin vivo.Nature 348166–168.

    Google Scholar 

  • Safer, D., Elzinga, M., and Nachmias, V. T. (1991). Thymosinβ4 and Fx, an actin-sequestering peptide, are indistinguishable.J. Biol. Chem. 2664029–4032.

    Google Scholar 

  • Sambrook, J., Fritsch, E. F., and Maniatis, T. (1989). InMolecular Cloning, a Laboratory Manual, Vol. 1, Cold Springer Harbor Laboratory Press, Cold Spring Harbor, N.Y.

    Google Scholar 

  • Thé, H., De., Vivanco-Ruize, M. D. M., Tiollais, P., Stunnenberg, H., and Dejean, A. (1990). Identification of a retinoic acid responsive element in the retinoic acid receptor-β gene.Nature 343177–180.

    Google Scholar 

  • Thomas, P. (1980). Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose.Proc. Natl. Acad. Sci. 775201–5205.

    Google Scholar 

  • Zelent, A., Krust, A., Petrovich, M., Kastner, P., and Chambon, P. A. (1989). Cloning of murineα andβ retinoic acid receptors and a novel receptorγ predominantly expressed in skin.Nature 339714–717.

    Google Scholar 

  • Zelent, A., Mendelsohn, C., Kastner, P., Krust, A., Garnier, J.-M., Ruffenach, F., Leroy, P., and Chambon, P. (1991). Differentially expressed isoforms of the mouse retinoic acid receptorβ are generated by usage of two promoters and alternative splicing.EMBO J. 1071–81.

    Google Scholar 

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Hall, A.K. Retinoids and a retinoic acid receptor differentially modulate thymosinβ 10 gene expression in transfected neuroblastoma cells. Cell Mol Neurobiol 12, 45–58 (1992). https://doi.org/10.1007/BF00711638

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  • DOI: https://doi.org/10.1007/BF00711638

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