Summary
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1.
Neuroblastoma (NB) is an unusual neuroectodermal tumor showing a high degree of spontaneous regression. NB cells can be induced to differentiatein vitro by various agents. Cell differentiation results in morphological changes characteristic of the mature neuronal phenotype, including outgrowth of neuritelike structures with several interconnections.
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2.
Recent experiments indicate that morphological differentiation of NB cells is associated with changes in expression of N-myc, c-myc, and c-myb oncogenes and synthesis of neurofilament proteins. However, little is known about the transcription of neurofilament genes during differentiation.
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3.
We have analyzed the expression of both the N-myc oncogene and mid-size neurofilament (NF) genes in the LAN-1 human NB cell line, cultured in the presence of retinoic acid (RA). Continuous treatment with RA induced morphological differentiation within 5–6 days. The transcription of N-myc was down-modulated within 24 hr of the initial exposure to RA. The mid-size NF mRNA was increased at this time. The expression of N-myc was not modified in serum-deprived LAN-1 cells, indicating that N-myc transcription is unaffected by the arrest of the cells in the G1 phase.
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4.
We conclude that new synthesis of mid-size NF mRNA and a decrease in N-myc transcription precedede novo formation of neurite-like processes and morphological cell differentiation of neuroblastoma cells.
References
Ausubel, F. M., Brent, R., Kingston, R. E., Moore, D. D., Smith, J. A., Seidman, J. G., and Struhl, K. (Eds.) (1987). Preparation and analysis of RNA. InCurrent Protocols in Molecular Biology 1987–88, Greene Associates and Wiley Interscience, New York, pp. 491–498.
Balmain, A., and Birnie, G. D. (1979). Nick translation of mammalian DNA.Biochim. Biophys. Acta 561155–166.
Bennet, G. S. (1987). Changes in intermediate filament composition during neurogenesis. In Hunt, R. K. (Ed.),Current Topics in Developmental Biology, Vol. 21. Neural Development, Part IV. Cellular and Molecular Differentiation, LTD Academic Press, London, pp. 151–183.
Biedler, J. L., Spengler, B. A., Chang, T., and Ross, R. A. (1988). Transdifferentiation of human neuroblastoma cells results in coordinate loss of neuronal and malignant properties. In Evans, A. E., D'Angio, G. J., Knudson, A. G., and Seeger, R. C. (Eds.),Advances in Neuroblastoma Research 2. Progress in Clinical and Biological Research, Vol. 271, Alan R. Liss, New York, pp. 265–276.
Cornaglia-Ferraris, P., and Tonini, G. P. (1988). Letters to the Editor.Am. J. Pediat. Hematol. Oncol. 10(2):182–183.
Cushing, H., and Wohlbach, B. B. (1927). The transformation of a malignant paravertebral sympathicoblastoma into a benign ganglioneuroma.Am. J. Pathol. B 202-215.
D'Angio, G. J., Evans, A. E., and Koop, C. E. (1971). Special pattern of widespread neuroblastoma with a favourable prognosis.Lancet 11046–1049.
Denk, H., Weybora, Ratschak, A., Sohar, R., and Franke, W. W. (1985). Distribution of vimentin, cytokeratins, and dyshomogeneal plaque proteins in human nephroblastomas as revealed by specific antibodies: Co-existence of cell groups of different degrees of epithelial differentiation.Differentiation 2988–97.
Evans, A. E., D'Angio, G. J., and Randolf, J. (1971). A proposed staging for children with neuroblastoma.Cancer 27374–378.
Feinberg, A. P., and Vogelstein, B. (1983). A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity.Anal. Biochem. 1326–13.
Feinberg, A. P., and Vogelstein, B. (1984). A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Addendum.Anal. Biochem. 137266–267.
Feramisco, J. R., Helman, D. M., Smart, J. E., Burridge, K., and Thomas, G. P. (1982). Isolation of total cellular RNA. In Maniatis, T., Fritsch, E. F., and Sambrook, J. (Eds.)Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 194.
Franke, W. W., Schmid, E., Schiller, D. L., Winter, S., Jarash, E. D., Mall, R., Denk, H., Jackson, B. W., and Illmensee, K. (1982). Differentiation related patterns of expression of proteins of intermediate-size filaments in tissues and cultured cells.Cold Spring Harbor Symp. Quant. Biol. 46431–453.
Grady, E. F., Schwab, M., and Rosenau, W. (1987). Expression of N-myc and c-src during the development of fetal human brain.Cancer Res. 472931–2936.
Hammerling, V., Bjelfman, C., and Pahlman, S. (1987). Different regulation of N- and c-myc expression during phorbole esther-induced maturation of human SH-SY5Y neuroblastoma cells.Oncogene 273–77.
Hill, B. T. (1986). Neuroblastoma. An overview of laboratory studies aimed at inducing tumor regression by initiation of differentiation or administration of antitumor drugs.Pediatric Hematology and Oncology, Hemisphere, Washington, D.C., pp. 73–88.
Hirschhorn, R. R., Marashi, F., Baserga, R., Stein, J., and Stein, G. (1984). Expression of histone genes in a G1-specific temperature-sensitive mutant of the cell cycle.Biochemistry 233731–3735.
Kelly, R. B., Carrarelli, N. R., Deutscher, M. P., Lehman, I. R. and Kornberg, A. (1970). Enzymatic synthesis of deoxyribonucleic acid. XXXII. Replication of duplex deoxyribonucleic acid by polymerase at a single strand break.J. Biol. Chem. 24539–45.
Kohl, N. E., Kanda, N., Schreck, R. R., Bruns, G., Latt, S. A., Gilbert, F., and Alt, W. F. (1983). Transposition and ampification of oncogene-related sequence in human neuroblastomas.Cell 35359–367.
Kohl, N. E., Legouy, E., De Pinho, R. A., Nisen, P. D., Smith, R. K., Gee, C. E., and Alt, F. W. (1986). Human N-myc is closely related in organization and nucleotide sequence to c-myc.Nature 31973–77.
Jakobovits, A., Schwab, M., Bishop, J. M., and Martin, G. R. (1985). Expression of N-myc in teratocarcinoma stern cells and mouse embryos.Nature 318188–191.
Lazarides, E. (1982). Intermediate filaments: A chemically heterogeneous developmentally regulated class of proteins.Annu. Rev. Biochem. 51219–250.
Maniatis, T., Fritsch, E. F., and Sambrook, J. (1982).Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., pp. 93–94.
Myers, M. W., Lazzarini, R. A., Lee, V. M.-Y., Schaepfer, W. W., and Nelson, D. L. (1987). The human mid-size neurofilament subunit, a repeated protein sequence and the relationship of its gene to the intermediate filament gene family.EMBO J. 61617–1626.
Nakano, T., Nagatsu, T., and Higashida, H. (1985). Expression of A and B types of monoamine oxidase in differentiated neuroblastoma hybrid cells.J. Neurochem. 4755–758.
Parodi, M. T., Varesio, L., and Tonini, G. P. (1989a). Morphological change and cellular differentiation induced by cisplatin in human neuroblastoma cell lines.Cancer Chemother. Pharmacol. 25114–116.
Parodi, M. T., Cornaglia-Ferraris, P., and Ponzoni, M. (1989b). Effects of gamma interferon on the growth, morphology and membrane and cytoskeletal protein expression of LAN-1 cells.Exp. Cell Res. 185327–341.
Phalman, S., Odelstad, L., Larsson, E., Grotte, G., and Nilsson, K. (1981). Phenotypic changes of human neuroblastoma cells in culture induced by 12-0-Tetradecanoyl-phorbol-13-acetate.Int. J. Cancer 28583–589.
Plumb, M., Stein, J., and Stein, G. (1983). Coordinate regulation of multiple histone mRNAs during the cell cycle in HeLa cells.Nucleic Acids Res. 11(8):2391–2410.
Ponzoni, M., Melodia, A., Cirillo, C., Casalaro, A., and Cornaglia-Ferraris, P. (1988). Effect of cytosine arabinoside on the growth and phenotypic expression of GIMEN, a new human neuroblastoma cell line. In Evans, A. E., D'Angio, G. J., Knudson, A. G., and Seegers, R. C. (Eds.),Advances in Neuroblastoma Research 2. Progress in Clinical and Biological Research, Vol. 271, Alan R. Liss, New York, pp. 437–448.
Real, F. X., Rettig, W. J., Chesa, P. G., Melamed, M. R., Old, L. J., and Mendelsohn, J. (1986). Expression of epidermal growth factor receptor in human cultured cells and tissues: Relationship to cell lineage and stage of differentiation.Cancer Res. 464726–4731.
Rettig, W. J., Spengler, B. A., Chesa, P. G., Old, L. J., and Biedler, J. L. (1987). Coordinate changes in neuronal phenotype and surface antigen expression in human neuroblastoma cell variants.Cancer Res. 471383–1389.
Ross, R. A., Ciccarone, V., Meyers, M. B., Spengler, B. A., and Biedler, J. L. (1988). Differential expression of intermediate filaments and fibromentin in human neuroblastoma cells. In Evans, A. E., D'Angio, G. J., Knudson, A. G., and Seeger, R. C. (Eds.),Advances in Neuroblastoma Research 2. Progress in Clinical and Biological Research, Vol. 271, Alan R. Liss, New York, pp. 277–289.
Seeger, R. C., Brodeur, G. M., Sather, H., Dalton, A., Siegel, S. E., Wong, K. Y., and Hammond, D. (1985). Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas.N. Engl. J. Med. 3131111–1116.
Seeger, R. C., Wada, R., Brodeur, G. M., Moss, T. J., Bjork, R. L., Sousa, L., and Slamon, D. J. (1988). Expression of N-myc by neuroblastomas with one or multiple copies of the oncogene. In Evans, A. E., D'Angio, G. J., Knudson, A. G. and Seeger, R. C. (Eds.),Advances in Neuroblastoma Research 2. Progress in Clinical and Biological Research, Vol. 271, Alan R. Liss, New York, pp. 41–49.
Shaw, G., and Weber, K. (1982). Differential expression of neurofilament triplet proteins in brain development.Nature 298277–279.
Schwab, M., Alitalo, K., Klempnauer, K. H., Varmus, H. E., Bishop, J. M., Gilbert, F., Brodeur, G. M., Goldstein, M., and Trent, J. (1983). Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumor.Nature 305245–248.
Sidell, N. (1982). Retinoic acid-induced growth inhibition and morphologic differentiation of human neuroblastoma cells in vitro.J. Natl. Cancer Inst.,68589–593.
Sidell, N., Altman, A., Hassler, M. R., and Seeger, R. C. (1983). Effects of retinoic acid (RA) on the growth and phenotypic expression of several human neuroblastoma cell lines.Exp. Cell Res. 14821–30.
Steinert, P. M., Jones, J. C. R., and Goldman, R. D. (1984). Intermediate filaments.J. Cell. Biol. 9922–27.
Thiele, C. J., Reynolds, C. P., and Israel, M. A. (1985). Decreased expression of N-myc precedes retinoic acid-induced morphological differentiation of human neuroblastoma.Nature 313404–406.
Tonini, G. P., Verdona, G., De Bernardi, B., Sansone, R., Massimo, L., and Cornaglia-Ferraris, P. (1987a). N-myc oncogene amplification in a patient with IV-S neuroblatoma.Am. J. Pediat. Hematol./Oncol. 9(18–10.
Tonini, G. P., Verdona, G., Garaventa, A., and Cornaglia-Ferraris, P. (1987b). Antiblastic treatment does not affect N-myc gene amplification in neuroblastoma.Anticancer Res. 7729–732.
Verdona, G., Garaventa, A., De Bernardi, B., Sansone, R., Di Martino, D., Cornaglia-Ferraris, P., and Tonini, G. P. (1986). N-myc amplification in neuroblastoma III and IV stages: Relation with other tumoral markers of disease.J. Tum. Mark. Oncol. 1(2):105–110.
Young, J. L., Ries, L. G., Silverberg, E., Horm, J. W., Miller, R. W. (1986). Cancer incidence, survival, and mortality for children younger than age 15 years.Cancer 58598–602.
Zimmermann, K. A., Yancopoulos, G. D., Collum, R. G., Smith, R. K., Kohl, N. E., Denis, K. A., Nau, M. M., Witte, O., Toran-Allerand, D., Gee, C. E., Minna, J. D., and Alt, F. (1986). Differential expression of myc-family genes during murine development.Nature 319780–783.
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Di Martino, D., Ponzoni, M., Cornaglia-Ferraris, P. et al. Different regulation of mid-size neurofilament and N-myc mRNA expression during neuroblastoma cell differentiation induced by retinoic acid. Cell Mol Neurobiol 10, 459–470 (1990). https://doi.org/10.1007/BF00711187
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DOI: https://doi.org/10.1007/BF00711187