ras Oncogenes pp 175-189 | Cite as

Expression of ras, myc and fos Oncogenes During the DMSO-Induced Detransformation of a Colon Carcinoma Line (HT29)

  • Susan A. Newbould
  • I. Gibson


The effects of differentiating agents on cancer cells are of considerable interest, both from a therapeutic viewpoint and as a means of elucidating the underlying mechanisms of cell transformation. A number of cell systems have been used to study the phenomenon of malignant cell detransformation and differentiation, in particular the HL-60 human promyelocytic leukemia line which can mature along either a granulocytic or monocytic pathway (1). Other workers have investigated differentiation of murine neuroblastoma cells (2), murine rhabdomyosarcoma cells (3), human melanocytes (4) and human colon carcinoma cells (5–14).


HT29 Cell Sodium Butyrate Human Colon Carcinoma Cell Human Colon Cancer Cell Line Human Colon Carcinoma Cell Line 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. (1).
    S. J. Collins, F. W. Ruscetti, R. E. Gallagher, and R. C. Gallo, Terminal differentiation of human promyelocytic leukemia cells induced by dimethylsulfoxide and other polar compounds, Proc. Natl. Acad. Sci. USA 75: 2458 (1978).PubMedCrossRefGoogle Scholar
  2. (2).
    Y. Kimhi, C. Palfrey, I. Spector, Y. Barak and U. Z. Littauer, Maturation of neuroblastoma cells in the presence of dimethylsulphoxide, Proc. Natl. Acad. Sci. USA 73: 462 (1976).PubMedCrossRefGoogle Scholar
  3. (3).
    D. L. Dexter, N,N-Dimethylformamide-induced morphological differentiation and reduction of tumorigenicity in cultured mouse rhabdomyosarcoma cells. Cancer Res. 37: 3136 (1977).PubMedGoogle Scholar
  4. (4).
    E. Huberman, C. Heckman, and R. Langenbach, Stimulation of differentiated functions in human melanoma cells by tumor-promoting agents and dimethyl sulphoxide, Cancer Res. 39: 2618 (1979).PubMedGoogle Scholar
  5. (5).
    D. L. Dexter, J. A. Barbosa and P. Calabresi, N,N-Dimethylformamide-induced alteration of cell culture characteristics and loss of tumorigenicity in cultured human colon carcinoma cells, Cancer Res. 39: 1020 (1979).PubMedGoogle Scholar
  6. (6).
    D. L. Dexter and J. C. Hager, Maturation-induction of tumor cells using a human colon carcinoma model, Cancer 45: 1178 (1980).PubMedCrossRefGoogle Scholar
  7. (7).
    J. C. Hager, D. V. Gold, J. A. Barbosa, Z. Fligiel, F. Miller and D. L. Dexter, N,N-Dimethylformamide-induced modulation of organ- and tumor-associated markers in cultured human colon carcinoma cells, J. Natl. Cancer Inst. 64: 439 (1980).PubMedGoogle Scholar
  8. (8).
    Y. S. Kim, D. Tsao, B. Siddiqui, J. S. Whitehead, P. Arnstein, J. Bennett and J. Hicks, Effects of sodium butyrate and dimethyl-sulphoxide on biochemical properties of human colon cancer cells, Cancer 45: 1185 (1980).PubMedCrossRefGoogle Scholar
  9. (9).
    A. Morita, D. Tsao and Y. S. Kim, Effect of sodium butyrate on alkaline phosphatase in HRT-18, a human rectal cancer cell line, Cancer Res. 42: 4540 (1982).PubMedGoogle Scholar
  10. (10).
    D. Tsao, A. Morita, A. Bella, P. Luu and Y. S. Kim, Differential effects of sodium butyrate, dimethyl sulfoxide and retinoic acid on membrane-associated antigen, enzymes and glycoproteins of human rectal adenocarcinoma cells, Cancer Res. 42: 1052 (1982).PubMedGoogle Scholar
  11. (11).
    M. Pinto, S. Robine-Leon, M-D. Appay, M. Kedinger, N. Triadou, E. Dussaulx, B. Lacroix, P. Simon-Assmann, K. Haffen, J. Fogh and A. Zweibaum, Enterocyte-like differentiation and polarization of the human colon carcinoma cell line CaCO-2 in culture, Biol. Cell 47: 323 (1983).Google Scholar
  12. (12).
    Y. S. Chung, I. S. Song, R. H. Erickson, M. H. Sleisenger and Y. S. Kim, Effect of growth and sodium butyrate on brush border membrane-associated hydrolases in human colorectal cancer cell lines, Cancer Res. 45: 2976 (1985).PubMedGoogle Scholar
  13. (13).
    M. Rousset, The human colon carcinoma cell lines HT29 and CaCO-2: two in vitro models for the study of intestinal differentiation, Biochimie 68: 1035 (1986).PubMedCrossRefGoogle Scholar
  14. (14).
    I. Chantret, A. Barbat, E. Dussaulx, M. Brattain, and A. Zweibaum, Epithelial polarity, villin expression and enterocytic differentiation of cultured human colon carcinoma cells: a survey of twenty cell lines, Cancer Res. 48: 1936 (1988).PubMedGoogle Scholar
  15. (15).
    M. Pinto, M-D. Appay, P. Simon-Assmann, G. Chevalier, N. Dracopoli, J. Fogh and A. Zweibaum, Enterocytic differentiation of cultured human colon cancer cells by replacement of glucose by galactose in the medium. Biol Cell 44: 193 (1982).Google Scholar
  16. (16).
    B. M. Wice, G. Trugman, M. Pinto, M. Rousset, G. Chevalier, E. Dussaulx, B. Lacroix and A. Zweibaum, The intracellular accumulation of UDP-N-acetylhexosamines is concomitant with the inability of human colon cancer cells to differentiate, J. Biol. Chem. 260: 139 (1985).PubMedGoogle Scholar
  17. (17).
    E. Chastre, S. Emami, G. Rosselin and C. Gespach, Vasoactive intestinal peptide receptor activity and specificity during enterocyte-like differentiation and retrodifferentiation of the human colonic cancerous subclone HT29–18, FEBS Lett 188: 197 (1985).PubMedCrossRefGoogle Scholar
  18. (18).
    A. Zweibaum, M. Pinto, G. Chevalier, E. Dussaulx, N. Triadou, B. Lacroix, K. Haffen, J.-L. Brun and M. Rousset, Enterocytic differentiation of a subpopulation of the human colon tumor cell line HT-29 selected for growth in sugar-free medium and its inhibition by glucose, J. Cell. Physiol. 122:21 (1985).PubMedCrossRefGoogle Scholar
  19. (19).
    F. Herz, A. Schermer, M. Halwer and L. H. Bogart, Alkaline phosphatase in HT-29, a human colon cancer cell line: influence of sodium butyrate and hyperosmolality, Arch. Biochem. Biophys. 210:581 (1981).CrossRefGoogle Scholar
  20. (20).
    F. Herz and M. Halwer, Synergistic induction of alkaline phosphatase in colonic carcinoma cells by sodium butyrate and hyperosmolality, Biochim. Biophys. Acta 718:220 (1982).CrossRefGoogle Scholar
  21. (21).
    B. Czerniak, F. Herz, R. P. Wersto and L. G. Koss, Modification of Ha-ras oncogene p21 expression and cell cycle progression in the human colonic cancer cell line HT-29, Cancer Res. 47:2826 (1987).PubMedGoogle Scholar
  22. (22).
    C. Augeron and C. L. Laboisse, Emergence of permanently differentiated cell clones in a human colonic cancer cell line in culture after treatment with sodium butyrate, Cancer Res. 44:3961 (1984).PubMedGoogle Scholar
  23. (23).
    C. Huet, C. Sahuquillo-Merino, E. Coudrier and D. Louvard, Absorptive and mucus-secreting subclones isolated from a multipotent intestinal cell line (HT29) provide new models for cell polarity and terminal differentiation, J. Cell. Biol. 105:345 (1987).PubMedCrossRefGoogle Scholar
  24. (24).
    B. Dudouet, S. Robine, C. Huet, C. Sahuquillo-Merino, L. Blair, E. Coudrier and D. Louvard, Changes in villin synthesis and subcellular distribution during intestinal differentiation of HT29–18 clones, J. Cell Biol. 105:359 (1987).PubMedCrossRefGoogle Scholar
  25. (25).
    A. Zweibaum, N. Triadou, M. Kedinger, C. Augeron, S. Robine-Leon, M. Pinto, M. Rousset and K. Haffen, Sucrase-isomaltase: a marker of foetal and malignant epithelial cells of the human colon, Int. J. Cancer 32:407 (1983).PubMedCrossRefGoogle Scholar
  26. (26).
    A. Zweibaum, H.-P. Hauri, E. Sterchi, I. Chantret, K. Haffen, J. Bamat and B. Sordat, Immunohistological evidence, obtained with monoclonal antibodies, of small intestinal brush border hydrolases in human colon cancers and foetal colons, Int. J. Cancer 34:591 (1984).PubMedCrossRefGoogle Scholar
  27. (27).
    A. Zweibaum, Enterocytic differentiation of cultured human colon cancer cell lines: negative modulation by D-glucose, in: “Ion Gradient-Coupled Transport” INSERM Symposium No.26 F. Alvarado and C. H. van Os, eds. Elsevier Science Publishers B. (1986).Google Scholar
  28. (28).
    C. J. Marshall, Oncogenes, J. Cell. Sci. Suppl. 4:417 (1986).Google Scholar
  29. (29).
    S. Nishimura and T. Sekiya, Human cancer and cellular oncogenes, Biochem. J. 243:313 (1987).PubMedGoogle Scholar
  30. (30).
    J. Fogh and G. Trempe, New human tumor cell lines, in: “Human Tumor cells in Vitro,” J. Fogh, ed., Plenum Press, New York (1975).CrossRefGoogle Scholar
  31. (31).
    R. I. Freshney, “Culture of animal cells,” Alan R. Liss, Inc., New York (1983).Google Scholar
  32. (32).
    H. Faulstich, H. Trischmann and D. Mayer, Preparation of Tetramethylrhodaminyl-phalloidin and uptake of the toxin into short-term cultured hepatocytes by endocytosis, Exp. Cell Res. 144:73 (1983).PubMedCrossRefGoogle Scholar
  33. (33).
    P. J. Harwood, D. W. Britton, P. J. Southall, G. M. Boxer, G. Rawlins and G. T. Rogers, Mapping epitope characteristics on carcinoembryonic antigen, Br. J. Cancer 54: 75 (1986).PubMedCrossRefGoogle Scholar
  34. (34).
    H. P. Hauri, E. E. Sterchi, D. Bienz, J. A. Fransen and A. Marxer, Expression and intracellular transport of microvillus membrane hydrolases in human intestinal epithelial cells, J. Cell Biol. 101: 838 (1985).PubMedCrossRefGoogle Scholar
  35. (35).
    J. P. Moore, D. C. Hancock, T. D. Littlewood and G. I. Evan, A sensitive and quantitative enzyme-linked immunosorbence assay for the c-myc and N-myc oncoproteins, Oncogene Res. 2: 65 (1987).PubMedGoogle Scholar
  36. (36).
    J. P. Moore and G. I. Evan, Immunoassays for oncoproteins, Nature 327: 733 (1987).CrossRefGoogle Scholar
  37. (37).
    D. M. Tidd, P. Hawley, H. M. Warenius and I. Gibson, Evaluation of N-ras oncogene antisense, sense and nonsense sequence methylphosphonate oligonucleotide analogues, Anti-Cancer Drug Design 3: 117 (1988).PubMedGoogle Scholar
  38. (38).
    D. J. Capon, E. Y. Chen, A. D. Levinson, P H. Seeburg and D. V. Goeddel, Complete nucleotide sequences of the T24 human bladder carcinoma oncogene and its normal homologue, Nature 302: 33 (1983).PubMedCrossRefGoogle Scholar
  39. (39).
    M. J. Murray, J. M. Cunningham, L. F. Parada, F. Dautry, P. Lebowitz and R. A. Weinberg, The HL-60 transforming sequence: A ras oncogene coexisting with altered myc genes in hematopoietic tumors, Cell 33: 749 (1983).PubMedCrossRefGoogle Scholar
  40. (40).
    M. S. McCoy, C. I. Bargmann and R. A. Weinberg, Human-colon carcinoma Ki-ras2 oncogene and its corresponding proto-oncogene, Mol.Cell.Biol. 4: 1577 (1984).PubMedGoogle Scholar
  41. (41).
    T. H. Rabbitts, A. Forster, P. Hamlyn and R. Baer, Effect of somatic mutation within translocated c-myc genes in Burkitt’s lymphoma, Nature 309: 592 (1984).PubMedCrossRefGoogle Scholar
  42. (42).
    R. Treisman, Transient accumulation of c-fos RNA following serum stimulation requires a conserved 5′ element and c-fos 3′ sequences, Cell 42: 889 (1985).PubMedCrossRefGoogle Scholar
  43. (43).
    L. W. Coggins, G. J. Grindlay, J. K. Vass, A. A. Slater, P. Montague, M. A. Stinson and J. Paul, Repetitive DNA sequences near 3 human beta-type globin genes, Nuc. Acids Res. 8: 3319 (1980).CrossRefGoogle Scholar
  44. (44).
    P. Linstead, B. Jennings, A. Prescott, P. Hawley, R. Warn and I. Gibson, Scanning electron microscopy and the transformed phenotype, Micron et Microscopica Acta 19: 155 (1988).CrossRefGoogle Scholar
  45. (45).
    J. Schmitz, H. Preiser, D. Maestracci, B. K. Ghosh, J. J. Cerda and R. K. Crane, Purification of the human intestinal brush border membrane, Biochim. Biophys. Acta 323: 98 (1973).CrossRefGoogle Scholar
  46. (46).
    A. Garen and C. Levinthal, A fine-structure genetic and chemical study of the enzyme alkaline phosphatase of E. Coli. I. Purification and characterization of alkaline phosphatase Biochim. Biophys. Acta 38: 470 (1960).PubMedCrossRefGoogle Scholar
  47. (47).
    D. L. Dexter, G. W. Crabtree, J. P. Stoeckler, T. M. Savarese, L. Y. Ghoda, T. L. Rogler-Brown, R. E. Parks and P. Calabresi, N,N-dimethylformamide and sodium butyrate modulation of the activities of purine-metabolizing enzymes in cultured human colon carcinoma cells, Cancer Res. 41: 808 (1981).PubMedGoogle Scholar
  48. (48).
    G. H. Lyman, H. D. Preisler and D. Papahadjopoulos, Membrane action of DMSO and other chemical inducers of Friend leukaemic cell differentiation, Nature 262:360 (1976).CrossRefGoogle Scholar
  49. (49).
    S. H. C. Ip and R. A. Cooper, Decreased membrane fluidity during differentiation of human promyelocytic leukemia cells in culture, Blood 56: 227 (1980).PubMedGoogle Scholar
  50. (50).
    G. Vidali L. C. Boffa, E. M. Bradbury and V. G. Allfrey, Butyrate suppression of histone deacetylation leads to accumulation of multiacetylated forms of histones H3 and H4 and increased DNase I sensitivity of the associated DNA sequences, Proc. Natl. Acad. Sei. USA 75: 2239 (1978).CrossRefGoogle Scholar
  51. (51).
    R. Reeves and P. Cserjesi, Sodium butyrate induces new gene expression in Friend erythroleukemic cells, J. Biol. Chem. 254:4283 (1979).PubMedGoogle Scholar
  52. (52).
    H. Denk, G. Tappeiner, R. Eckerstorfer and J. H. Holzner, Carcinoembryonic antigen (CEA) in gastrointestinal and extragastrointestinal tumors and its relationship to tumor-cell differentiation, Int. J. Cancer 10: 262 (1972).PubMedCrossRefGoogle Scholar
  53. (53).
    J. Breborowicz, G. C. Easty and A. M. Neville, The production of carcinoembryonic antigen (CEA) by human colonic carcinomas and normal colonic mucosa in monolayer and organ culture, Ann. Immunol. 124: 613 (1973).Google Scholar
  54. (54).
    A. Leibovitz, J. C. Stinson, W. B. McCombs, C. E. McCoy, K. C. Mazur and N. D. Mabry, Classification of human colorectal adenocarcinoma cell lines, Cancer Res. 36:4562 (1976).PubMedGoogle Scholar
  55. (55).
    Z. R. Shi, D. Ts ao and Y. S. Kim, Subce11ular distribution, synthesis, and release of carcinoembryonic antigen in cultured human colon adenocarcinoma cell lines, Cancer Res. 43: 4045 (1983).PubMedGoogle Scholar
  56. (56).
    M. Perucho, M. Goldfarb, K. Shimizu, C. Lama, J. Fogh and M. Wigler, Human-Tumor-Derived cell lines contain common and different transforming genes, Cell 27: 467 (1981).PubMedCrossRefGoogle Scholar
  57. (57).
    K. Fujita, N. Ohuchi, T. Yao, M. Okumara, Y. Fukushima, Y. Kanakura, Y. Kitamura and J. Fujita, Frequent overexpression, but not activation by point mutation, of ras genes in primary human gastric cancers, Gastroenterology 93: 1339 (1987).PubMedGoogle Scholar
  58. (58).
    J. R. Feramisco, M. Gross, T. Kamata, M. Rosenberg and R. W. Sweet, Microinjection of the oncogene form of the human H-ras (T-24) protein results in rapid proliferation of quiescent cells, Cell 38: 109 (1984).PubMedCrossRefGoogle Scholar
  59. (59).
    D. W. Stacey and H-F Kung, Transformation of NIH-3T3 cells by microinjection of Ha-ras p21 protein, Nature 310: 508 (1984).PubMedCrossRefGoogle Scholar
  60. (60).
    J. R. Feramisco, R. Clark, G. Wong, N. Arnheim, R. Milley and F. McCormick, Transient reversion of ras oncogene-induced cell transformation by antibodies specific for amino acid 12 of ras protein, Nature 314: 639 (1985).PubMedCrossRefGoogle Scholar
  61. (61).
    L. S. Mulcahy, M. R. Smith and D. W. Stacey, Requirement for ras proto-oncogene function during serum-stimulated growth of NIH 3T3 cells, Nature 313: 241 (1985)PubMedCrossRefGoogle Scholar
  62. (62).
    L. H. Augenlicht, C. Augeron, G. Yander and C. Laboisse, Overexpression of ras in mucus-secreting human colon carcinoma cells of low tumorigenicity, Cancer Res. 47: 3763 (1987).PubMedGoogle Scholar
  63. (63).
    P. Garin-Chesa, W. J. Rettig, M. R. Melamed, L. J. Old and H. L. Niman, Expression of p2lras in normal and malignant human tissues: Lack of association with proliferation and malignancy, Proc. Natl. Acad. Sci, USA 84: 3234 (1987).CrossRefGoogle Scholar
  64. (64).
    S. Pfeifer-Ohlsson, A. S. Gronsten, J. Rydnert and 4 others, Spatial and temporal pattern of cellular myc oncogene expression in developing human placenta: Implications for embryonic cell proliferation, Cell 38: 585 (1984).PubMedCrossRefGoogle Scholar
  65. (65).
    J. Filmus and R. N. Buick, Relationship of c-myc expression to differentiation and proliferation of HL-60 cells, Cancer Res. 45:822 (1985).PubMedGoogle Scholar
  66. (66).
    L. E. Grosso and H. C. Pitot, Transcriptional regulation of c-myc during chemically induced differentiation of HL-60 cultures, Cancer Res. 45: 847 (1985).PubMedGoogle Scholar
  67. (67).
    R. J. Alexander, J. N. Buxbaum and R. F. Raicht, Oncogene alterations in primary human colon tumours, Gastroenterology 91: 1503 (1986)PubMedGoogle Scholar
  68. (68).
    K. Alitalo, M. Schwab, C. C. Lin, H. E. Varmus and J. M. Bishop, Homogeneously staining chromosomal regions contain amplified copies of an abundantly expressed cellular oncogene (c-myc) in malignant neuroendocrine cells from a human colon carcinoma, Proc. Natl. Acad. Sci. USA 80: 1707 (1983).PubMedCrossRefGoogle Scholar
  69. (69).
    E. L. Wickstrom, E. Wickstrom, G.H. Lyman and D. L. Freeman, HL-60 cell proliferation inhibited by an anti-c-myc pentadecadeoxynucleotide, Fed. Proc. 45: 1708 (1986).Google Scholar
  70. (70).
    J. T. Holt, R. L. Redner and A. W. Neinhuis, An oligomer complementary to c-myc inhibits proliferation of HL60 promyelocytic cells and induces differentiation, Mol.Cell.Biol. 8: 963 (1987).Google Scholar

Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • Susan A. Newbould
    • 1
  • I. Gibson
    • 1
  1. 1.School of Biological SciencesUniversity of East AngliaNorwichUK

Personalised recommendations