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. 1989 Jun;8(6):1793–1799. doi: 10.1002/j.1460-2075.1989.tb03573.x

The human L-myc gene is expressed as two forms of protein in small cell lung carcinoma cell lines: detection by monoclonal antibodies specific to two myc homology box sequences.

N Ikegaki 1, J Minna 1, R H Kennett 1
PMCID: PMC401025  PMID: 2548855

Abstract

The L-myc gene is the third member of the myc family of proto-oncogenes. Amplification and elevated expression of the L-myc gene has been detected in a subset of small cell lung carcinoma (SCLC) cell lines. The biological properties and functions of the L-myc gene and its product have not yet been elucidated. Monoclonal antibodies against two myc homology boxes were used to characterize the L-myc gene product. These antibodies react with two groups of polypeptides of apparent masses of 60, 61 and 66 kd (the long forms), and 34 and 37 kd (the short forms) in SCLC cells expressing L-myc transcripts. The long form L-myc proteins are associated with the nuclear fraction of the cells. The short form L-myc proteins are present in the cytoplasmic fraction, though diffusion of the short forms from the nucleus during cell fractionation cannot be ruled out. The half-life of the long form polypeptides is approximately 45-90 min. The short form polypeptides have a half-life of approximately 120-180 min. The L-myc protein is not detectable in the mitotic cells, suggesting that the L-myc protein expression is tightly regulated during the cell cycle.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alitalo K., Schwab M. Oncogene amplification in tumor cells. Adv Cancer Res. 1986;47:235–281. doi: 10.1016/s0065-230x(08)60201-8. [DOI] [PubMed] [Google Scholar]
  2. Classon M., Henriksson M., Sümegi J., Klein G., Hammarskjöld M. L., Hammaskjöld M. L. Elevated c-myc expression facilitates the replication of SV40 DNA in human lymphoma cells. Nature. 1987 Nov 19;330(6145):272–274. doi: 10.1038/330272a0. [DOI] [PubMed] [Google Scholar]
  3. Cole M. D. The myc oncogene: its role in transformation and differentiation. Annu Rev Genet. 1986;20:361–384. doi: 10.1146/annurev.ge.20.120186.002045. [DOI] [PubMed] [Google Scholar]
  4. Dang C. V., Lee W. M. Identification of the human c-myc protein nuclear translocation signal. Mol Cell Biol. 1988 Oct;8(10):4048–4054. doi: 10.1128/mcb.8.10.4048. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. De Greve J., Battey J., Fedorko J., Birrer M., Evan G., Kaye F., Sausville E., Minna J. The human L-myc gene encodes multiple nuclear phosphoproteins from alternatively processed mRNAs. Mol Cell Biol. 1988 Oct;8(10):4381–4388. doi: 10.1128/mcb.8.10.4381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DePinho R., Mitsock L., Hatton K., Ferrier P., Zimmerman K., Legouy E., Tesfaye A., Collum R., Yancopoulos G., Nisen P. Myc family of cellular oncogenes. J Cell Biochem. 1987 Apr;33(4):257–266. doi: 10.1002/jcb.240330404. [DOI] [PubMed] [Google Scholar]
  7. Dunn S. D. Effects of the modification of transfer buffer composition and the renaturation of proteins in gels on the recognition of proteins on Western blots by monoclonal antibodies. Anal Biochem. 1986 Aug 15;157(1):144–153. doi: 10.1016/0003-2697(86)90207-1. [DOI] [PubMed] [Google Scholar]
  8. Hann S. R., Eisenman R. N. Proteins encoded by the human c-myc oncogene: differential expression in neoplastic cells. Mol Cell Biol. 1984 Nov;4(11):2486–2497. doi: 10.1128/mcb.4.11.2486. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hann S. R., King M. W., Bentley D. L., Anderson C. W., Eisenman R. N. A non-AUG translational initiation in c-myc exon 1 generates an N-terminally distinct protein whose synthesis is disrupted in Burkitt's lymphomas. Cell. 1988 Jan 29;52(2):185–195. doi: 10.1016/0092-8674(88)90507-7. [DOI] [PubMed] [Google Scholar]
  10. Hann S. R., Thompson C. B., Eisenman R. N. c-myc oncogene protein synthesis is independent of the cell cycle in human and avian cells. 1985 Mar 28-Apr 3Nature. 314(6009):366–369. doi: 10.1038/314366a0. [DOI] [PubMed] [Google Scholar]
  11. Iguchi-Ariga S. M., Itani T., Kiji Y., Ariga H. Possible function of the c-myc product: promotion of cellular DNA replication. EMBO J. 1987 Aug;6(8):2365–2371. doi: 10.1002/j.1460-2075.1987.tb02513.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Iguchi-Ariga S. M., Okazaki T., Itani T., Ogata M., Sato Y., Ariga H. An initiation site of DNA replication with transcriptional enhancer activity present upstream of the c-myc gene. EMBO J. 1988 Oct;7(10):3135–3142. doi: 10.1002/j.1460-2075.1988.tb03180.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ikegaki N., Bukovsky J., Kennett R. H. Identification and characterization of the NMYC gene product in human neuroblastoma cells by monoclonal antibodies with defined specificities. Proc Natl Acad Sci U S A. 1986 Aug;83(16):5929–5933. doi: 10.1073/pnas.83.16.5929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kaye F., Battey J., Nau M., Brooks B., Seifter E., De Greve J., Birrer M., Sausville E., Minna J. Structure and expression of the human L-myc gene reveal a complex pattern of alternative mRNA processing. Mol Cell Biol. 1988 Jan;8(1):186–195. doi: 10.1128/mcb.8.1.186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kelly K., Cochran B. H., Stiles C. D., Leder P. Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor. Cell. 1983 Dec;35(3 Pt 2):603–610. doi: 10.1016/0092-8674(83)90092-2. [DOI] [PubMed] [Google Scholar]
  16. Kingston R. E., Baldwin A. S., Jr, Sharp P. A. Regulation of heat shock protein 70 gene expression by c-myc. Nature. 1984 Nov 15;312(5991):280–282. doi: 10.1038/312280a0. [DOI] [PubMed] [Google Scholar]
  17. Leder P., Battey J., Lenoir G., Moulding C., Murphy W., Potter H., Stewart T., Taub R. Translocations among antibody genes in human cancer. Science. 1983 Nov 18;222(4625):765–771. doi: 10.1126/science.6356357. [DOI] [PubMed] [Google Scholar]
  18. Little C. D., Nau M. M., Carney D. N., Gazdar A. F., Minna J. D. Amplification and expression of the c-myc oncogene in human lung cancer cell lines. Nature. 1983 Nov 10;306(5939):194–196. doi: 10.1038/306194a0. [DOI] [PubMed] [Google Scholar]
  19. Nau M. M., Brooks B. J., Battey J., Sausville E., Gazdar A. F., Kirsch I. R., McBride O. W., Bertness V., Hollis G. F., Minna J. D. L-myc, a new myc-related gene amplified and expressed in human small cell lung cancer. Nature. 1985 Nov 7;318(6041):69–73. doi: 10.1038/318069a0. [DOI] [PubMed] [Google Scholar]
  20. Nau M. M., Brooks B. J., Jr, Carney D. N., Gazdar A. F., Battey J. F., Sausville E. A., Minna J. D. Human small-cell lung cancers show amplification and expression of the N-myc gene. Proc Natl Acad Sci U S A. 1986 Feb;83(4):1092–1096. doi: 10.1073/pnas.83.4.1092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Persson H., Hennighausen L., Taub R., DeGrado W., Leder P. Antibodies to human c-myc oncogene product: evidence of an evolutionarily conserved protein induced during cell proliferation. Science. 1984 Aug 17;225(4663):687–693. doi: 10.1126/science.6431612. [DOI] [PubMed] [Google Scholar]
  22. Ramsay G., Evan G. I., Bishop J. M. The protein encoded by the human proto-oncogene c-myc. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7742–7746. doi: 10.1073/pnas.81.24.7742. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ramsay G., Stanton L., Schwab M., Bishop J. M. Human proto-oncogene N-myc encodes nuclear proteins that bind DNA. Mol Cell Biol. 1986 Dec;6(12):4450–4457. doi: 10.1128/mcb.6.12.4450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Roussel M., Saule S., Lagrou C., Rommens C., Beug H., Graf T., Stehelin D. Three new types of viral oncogene of cellular origin specific for haematopoietic cell transformation. Nature. 1979 Oct 11;281(5731):452–455. doi: 10.1038/281452a0. [DOI] [PubMed] [Google Scholar]
  25. Slamon D. J., Boone T. C., Seeger R. C., Keith D. E., Chazin V., Lee H. C., Souza L. M. Identification and characterization of the protein encoded by the human N-myc oncogene. Science. 1986 May 9;232(4751):768–772. doi: 10.1126/science.3008339. [DOI] [PubMed] [Google Scholar]
  26. Spector D. L., Watt R. A., Sullivan N. F. The v- and c-myc oncogene proteins colocalize in situ with small nuclear ribonucleoprotein particles. Oncogene. 1987 Mar;1(1):5–12. [PubMed] [Google Scholar]
  27. Stone J., de Lange T., Ramsay G., Jakobovits E., Bishop J. M., Varmus H., Lee W. Definition of regions in human c-myc that are involved in transformation and nuclear localization. Mol Cell Biol. 1987 May;7(5):1697–1709. doi: 10.1128/mcb.7.5.1697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]

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