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. 1988 Oct;8(10):4322–4327. doi: 10.1128/mcb.8.10.4322

Effect of cellular determination on oncogenic transformation by chemicals and oncogenes.

M A Harrington 1, F Gonzales 1, P A Jones 1
PMCID: PMC365505  PMID: 2460742

Abstract

Three developmentally determined myogenic cell lines derived from C3H 10T1/2 C18 (10T1/2) mouse embryo cells treated with 5-azacytidine were compared with the parental 10T1/2 line for their susceptibility to oncogenic transformation by 3-methylcholanthrene or the activated human c-Ha-ras oncogene. Neither the 10T1/2 cells nor the myogenic derivatives grew in soft agar or formed tumors in nude mice. In contrast to 10T1/2 cells, the three myogenic derivatives were not susceptible to transformation by 3-methylcholanthrene, so that cellular determination altered the response of 10T1/2 cells to chemical carcinogen. On the other hand, all cell types were transformed to a tumorigenic phenotype following transfection with the activated c-Ha-ras gene. The transfected myogenic cells expressed both the c-Ha-ras gene and the muscle determination gene MyoD1. In contrast to other reports, the presence of as many as six copies of the c-Ha-ras gene per genome did not prevent the formation of striated muscle cells which expressed immunologically detectable muscle-specific myosin. The expression of the c-Ha-ras gene does not therefore necessarily preclude the expression of the determination gene for myogenesis or prevent end-stage myogenic differentiation.

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Selected References

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

  1. Bader D., Masaki T., Fischman D. A. Immunochemical analysis of myosin heavy chain during avian myogenesis in vivo and in vitro. J Cell Biol. 1982 Dec;95(3):763–770. doi: 10.1083/jcb.95.3.763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bell J. C., Jardine K., McBurney M. W. Lineage-specific transformation after differentiation of multipotential murine stem cells containing a human oncogene. Mol Cell Biol. 1986 Feb;6(2):617–625. doi: 10.1128/mcb.6.2.617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Benedict W. F., Banerjee A., Gardner A., Jones P. A. Induction of morphological transformation in mouse C3H/10T1/2 clone 8 cells and chromosomal damage in hamster A(T1)C1-3 cells by cancer chemotherapeutic agents. Cancer Res. 1977 Jul;37(7 Pt 1):2202–2208. [PubMed] [Google Scholar]
  4. Bond V. C., Wold B. Poly-L-ornithine-mediated transformation of mammalian cells. Mol Cell Biol. 1987 Jun;7(6):2286–2293. doi: 10.1128/mcb.7.6.2286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chandler L. A., Ghazi H., Jones P. A., Boukamp P., Fusenig N. E. Allele-specific methylation of the human c-Ha-ras-1 gene. Cell. 1987 Aug 28;50(5):711–717. doi: 10.1016/0092-8674(87)90329-1. [DOI] [PubMed] [Google Scholar]
  6. Chapman A. B., Knight D. M., Dieckmann B. S., Ringold G. M. Analysis of gene expression during differentiation of adipogenic cells in culture and hormonal control of the developmental program. J Biol Chem. 1984 Dec 25;259(24):15548–15555. [PubMed] [Google Scholar]
  7. Church G. M., Gilbert W. Genomic sequencing. Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991–1995. doi: 10.1073/pnas.81.7.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Constantinides P. G., Jones P. A., Gevers W. Functional striated muscle cells from non-myoblast precursors following 5-azacytidine treatment. Nature. 1977 May 26;267(5609):364–366. doi: 10.1038/267364a0. [DOI] [PubMed] [Google Scholar]
  9. Constantinides P. G., Taylor S. M., Jones P. A. Phenotypic conversion of cultured mouse embryo cells by aza pyrimidine nucleosides. Dev Biol. 1978 Sep;66(1):57–71. doi: 10.1016/0012-1606(78)90273-7. [DOI] [PubMed] [Google Scholar]
  10. Davis R. L., Weintraub H., Lassar A. B. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell. 1987 Dec 24;51(6):987–1000. doi: 10.1016/0092-8674(87)90585-x. [DOI] [PubMed] [Google Scholar]
  11. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  12. Gadi I. K., Harrison J. J., Sager R. Genetic analysis of tumorigenesis: XVI. Chromosome changes in azacytidine- and insulin-induced tumorigenesis. Somat Cell Mol Genet. 1984 Sep;10(5):521–529. doi: 10.1007/BF01534856. [DOI] [PubMed] [Google Scholar]
  13. Hsiao W. L., Lopez C. A., Wu T., Weinstein I. B. A factor present in fetal calf serum enhances oncogene-induced transformation of rodent fibroblasts. Mol Cell Biol. 1987 Oct;7(10):3380–3385. doi: 10.1128/mcb.7.10.3380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jones P. A. Altering gene expression with 5-azacytidine. Cell. 1985 Mar;40(3):485–486. doi: 10.1016/0092-8674(85)90192-8. [DOI] [PubMed] [Google Scholar]
  15. Jones P. A., Laug W. E., Gardner A., Nye C. A., Fink L. M., Benedict W. F. In vitro correlates of transformation in C3H/10T1/2 clone 8 mouse cells. Cancer Res. 1976 Aug;36(8):2863–2867. [PubMed] [Google Scholar]
  16. Jones P. A., Taylor S. M. Cellular differentiation, cytidine analogs and DNA methylation. Cell. 1980 May;20(1):85–93. doi: 10.1016/0092-8674(80)90237-8. [DOI] [PubMed] [Google Scholar]
  17. Konieczny S. F., Emerson C. P., Jr 5-Azacytidine induction of stable mesodermal stem cell lineages from 10T1/2 cells: evidence for regulatory genes controlling determination. Cell. 1984 Oct;38(3):791–800. doi: 10.1016/0092-8674(84)90274-5. [DOI] [PubMed] [Google Scholar]
  18. Lassar A. B., Paterson B. M., Weintraub H. Transfection of a DNA locus that mediates the conversion of 10T1/2 fibroblasts to myoblasts. Cell. 1986 Dec 5;47(5):649–656. doi: 10.1016/0092-8674(86)90507-6. [DOI] [PubMed] [Google Scholar]
  19. Liu L., Harrington M., Jones P. A. Characterization of myogenic cell lines derived by 5-azacytidine treatment. Dev Biol. 1986 Oct;117(2):331–336. doi: 10.1016/0012-1606(86)90302-7. [DOI] [PubMed] [Google Scholar]
  20. Markert C. L. Neoplasia: a disease of cell differentiation. Cancer Res. 1968 Sep;28(9):1908–1914. [PubMed] [Google Scholar]
  21. Olson E. N., Spizz G., Tainsky M. A. The oncogenic forms of N-ras or H-ras prevent skeletal myoblast differentiation. Mol Cell Biol. 1987 Jun;7(6):2104–2111. doi: 10.1128/mcb.7.6.2104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Payne P. A., Olson E. N., Hsiau P., Roberts R., Perryman M. B., Schneider M. D. An activated c-Ha-ras allele blocks the induction of muscle-specific genes whose expression is contingent on mitogen withdrawal. Proc Natl Acad Sci U S A. 1987 Dec;84(24):8956–8960. doi: 10.1073/pnas.84.24.8956. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Reznikoff C. A., Bertram J. S., Brankow D. W., Heidelberger C. Quantitative and qualitative studies of chemical transformation of cloned C3H mouse embryo cells sensitive to postconfluence inhibition of cell division. Cancer Res. 1973 Dec;33(12):3239–3249. [PubMed] [Google Scholar]
  24. Reznikoff C. A., Brankow D. W., Heidelberger C. Establishment and characterization of a cloned line of C3H mouse embryo cells sensitive to postconfluence inhibition of division. Cancer Res. 1973 Dec;33(12):3231–3238. [PubMed] [Google Scholar]
  25. Schneider M. D., Perryman M. B., Payne P. A., Spizz G., Roberts R., Olson E. N. Autonomous expression of c-myc in BC3H1 cells partially inhibits but does not prevent myogenic differentiation. Mol Cell Biol. 1987 May;7(5):1973–1977. doi: 10.1128/mcb.7.5.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Taylor S. M., Jones P. A. Multiple new phenotypes induced in 10T1/2 and 3T3 cells treated with 5-azacytidine. Cell. 1979 Aug;17(4):771–779. doi: 10.1016/0092-8674(79)90317-9. [DOI] [PubMed] [Google Scholar]

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