Abstract
The molecular mechanisms reported to regulate the expression of the c-myc gene include gene amplification, transcriptional activation, a block to transcriptional elongation, and mRNA stability. We have investigated which of these mechanisms determine the striking variation in mRNA levels of the three myc family members (c-, N-, and L-myc) observed in human small cell lung cancer cells, a system in which all three genes are expressed at widely varying levels. Myc family gene amplification is frequently observed. However there are numerous examples of elevated expression for each of these genes without amplification. In these instances, a block to transcriptional elongation appears to be a significant regulatory mechanism controlling the steady-state levels of c-myc and L-myc mRNA, but not N-myc. When this block to elongation is relieved, elevated levels of c-myc and L-myc gene expression are observed in several cell lines in the absence of gene amplification. All primary transcription detected from c-, N-, and L-myc in a nuclear run-on assay results from RNA polymerase II’activity, with no detectable contribution of RNA polymerase III transcription observed.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Alt FW, Depinho R, Zimmerman K, Legouy E, Hatton K, Ferrier P, Tesfaye A, Yancopoulos GD, Nisen PD (1986) The human myc gene family. CSHCQB LI:931–941
Bentley DL, Groudine M (1986) A block to elongation is largely responsible for decreased transcription of c-myc in differentiated HL60 cells. Nature 321:702–706
Birrer MJ, Segal S, DeGreve JS, Kaye F, Sausville EA, Minna JD (1988) L-myc cooperates with ras to transform primary rat embryo fibroblasts. Mol.Cell.Biol., in press
Blanchard JM, Piechaczyk M, Dani C, Chambard JC, Franchi A, Pouyssegur J, Jeanteur P (1985) c-myc gene is transcribed at high rate in Go-arrested fibroblasts and is post-transcriptionally regulated in response to growth factors. Nature 317:443–445
Dean M, Levine RA, Campisi J (1986) c-myc regulation during retinoic acid-induced differentiation of F9 cells is post-transcriptional and associated with growth arrest. Mol. Cell. Biol. 6:518–524
Gazdar AF, Carney DN, Nau MM, Minna JD (1985) Characterization of variant subclasses of cell lines derived from small cell lung cancer having distinctive biochemical, morphological, and growth properties. Cancer Res. 45:2924–2930
Greenberg ME, Ziff EB (1984) Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene. Nature 311:433–438
Hayward WS, Neel BG, Astrin SM (1981) Activation of cellular onc genes by promoter insertion in ALV-induced lymphoid leukosis. Nature 290:475–479
Johnson BE, Battey JF, Linnoila I, Becken KL, Makuch RW, Snider RH, Carney DN, Minna JD (1986) Changes in the phenotype of human small cell lung cancer cell lines after transfection and expression of the c-myc proto-oncogene. J. Clin. Invest. 78:525–532
Johnson BE, Idhe DC, Makuch RW, Gazdar AF, Carney DN, Oie H, Russell E, Nau MM, Minna JD (1987) Myc family oncogene amplification in tumor cell lines established from small cell lung cancer patients and its relationship to clinical status and course. J. Clin. Invest. 79:1629–1634
Kelly K, Cochran BH, Stiles CD, Leder P (1983) Cell-specific regulation of the myc gene by lymphocyte mitogens and platelet-derived growth factor. Cell 35:603–610
Kohl NE, Kanda N, Shreck R, Bruns G, Latt S, Gilbert F (1983) Transposition and amplification of oncogene related sequence in human neuroblastomas. Cell 35:359–367
Krystal G, Birrer M, Way J, Nau MM, Sausville EA, Thompson C, Minna JD, Battey JF (1988) Multiple mechanisms for transcriptional regulation of the myc gene family in small cell lung cancer, manuscript submitted Land H, Parada LF, Weinberg R (1983) Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature 304:596–602
Leder P, Battey JF, Lenoir G, Moulding C, Murphy W, Potter H, Stewart T, Taub R (1983) Translocations among antibody genes in human cancer. Science 222:765–771
Lindell T, Weinberg F, Morris B, Roeder R, Rutter W (1970) Specific inhibition of RNA polymerase II by alpha-amanitin. Science 170:447–448.
Little CD, Nau MM, Carney DN, Gazdar AF, Minna JD (1983) Amplification and expression of the c-myc oncogene in human lung cancer cell lines. Nature 306:194–196
Mechti N, Piechaczyk M, Blanchard JM, Marty L, Bonnieu A, Jeanteur P, Lebleu B (1986) Transcriptional and post-transcriptional regulation of c-myc expression during the differentiation of murine erythroleukemia Friend cells. Nuc. Acids Res. 14:9653–9666
Minna JD, Battey JF, Brooks BJ, Cuttitta F, Gazdar AF, Johnson BE, Ihde DC, Lebacq-Verheyden AM, Mulshine J, Nau MM, Oie HK, Sausville EA, Seifter E, Vinocour M (1986) Molecular genetic analysis reveals chromosomal deletion, gene amplification, and autocrine growth factor production in the pathogenesis of human lung cancer. CSHSQB LI:843–853
Nau MM, Brooks BJ, Battey JF, Sausville EA, Gazdar AF, Kirsch IR, McBride OW, Bertness V, Hollis GF, Minna JD (1985) L-myc, a new myc-related gene amplified and expressed in human small cell lung cancer. Nature 318:69–73
Nau MM, Brooks BJ, Carney DN, Gazdar AF, Battey JF, Sausville EA, Minna JD (1986) Human small cell lung cancers show amplification and expression of the N-myc gene. Proc. Natl. Acad. Sci. USA 83:1092–1096
Nepveu A, Marcu KB (1986) Intragenic pausing and anti-sense transcription within the murine c-myc locus. EMBO 5:2859–2965
Schwab M, Alitalo K, Klempnauer L, Varmus H, Bishop JM, Gilbert F, Brodeur G, Goldstein M, Trent J (1983) Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumor. Nature 305:245–248
Schwab M, Varmus HE, and Bishop JM (1985) Human N-myc gene contributes to neoplastic transformation of mammalian cells in culture. Nature 316:160–162
Yancopoulous GD, Nisen PD, Tesfaye A, Kohl NE, Goldfarb MP, Alt F (1985) N-myc can cooperate with ras to transform normal cells in culture. Proc. Natl. Acad. Sci. USA 80:1195–1198
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1988 Springer-Verlag Berlin · Heidelberg
About this paper
Cite this paper
Krystal, G., Way, J., Battey, J. (1988). Comparison of c-, N-, and L-myc Transcriptional Regulation. In: Potter, M., Melchers, F. (eds) Mechanisms in B-Cell Neoplasia 1988. Current Topics in Microbiology and Immunology, vol 141. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-74006-0_37
Download citation
DOI: https://doi.org/10.1007/978-3-642-74006-0_37
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-74008-4
Online ISBN: 978-3-642-74006-0
eBook Packages: Springer Book Archive