Abstract
A common feature of follicular lymphoma, the most prevalent haematological malignancy in humans, is a chromosome translocation (t(14;18)) that has coupled the immunoglobulin heavy chain locus to a chromosome 18 gene denoted bcl-2 (refs 1–6). By analogy with the translocated c-myc oncogene in other B-lymphoid tumours (reviewed in ref. 7), bcl-2 is a candidate oncogene, but no biological effects of bcl-2 have yet been reported. To test whether bcl-2 influences the growth of haematopoietic cells, either alone or together with a deregulated c-myc gene, we have introduced a human bcl-2 complementary DNA (ref. 3) using a retroviral vector into bone marrow cells from either normal or Eµ-myc transgenic mice, in which B-lineage cells constitutively express the c-myc gene8–10. Bcl-2 cooperated with c-myc to promote proliferation of B-cell precursors, some of which became tumorigenic. To determine how bcl-2 expression impinges on growth factor requirements, the gene was introduced into a lymphoid and a myeloid cell line that require interleukin 3 (IL-3) (refs 11 and 12). In the absence of IL-3, bcl-2 promoted the survival of the infected cells but they persisted in a G0 state, rather than proliferating. These results argue that bcl-2 provided a distinct survival signal to the cell and may contribute to neoplasia by allowing a clone to persist until other oncogenes, such as c-myc, become activated.
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References
Tsujimoto, Y., Cossman, J., Jafle, E. & Croce, C. M. Science 226, 1097–1099 (1984).
Bakhshi, A. et al. Cell 41, 899–906 (1985).
Cleary, M. Smith, S. D. & Sklar, J. Cell 47, 19–28 (1986).
Seto, M et al. EMBO J. 7, 123–131 (1987).
Tsujimoto, Y., Ikegaki, N. & Croce, C. M. Oncogene 2, 3–7 (1987).
Graninger, W. B., Seto, M., Boutain, B., Goldman, P. & Korsmeyer, S. J. J. clin. Invest. 80, 1512–1515 (1987).
Cory, S. in Advances in Cancer Research Vol. 47 (eds Klein, G. & Weinhouse, S.) 189–234 (Harcourt Brace Jovanovich, Orlando, 1986).
Adams, J. M. et al. Nature 318, 533–538 (1985).
Langdon, W. Y., Harris, A. W., Cory, S. & Adams, J. M. Cell 47, 11–18 (1986).
Alexander, W. S., Schrader, J. W. & Adams, J. M. Molec. cell. Biol. 7, 1436–1444 (1987).
Palacios, R., Karasuyama, H. & Rolnick, A. EMBO J. 6, 3687–3693 (1987).
Dexter, T. M., Garland, J., Scott, D., Scolnick, E. & Metcalf, D. J. exp. Med. 152, 1036–1047 (1980).
Hariharan, I. K., Adams, J. M. & Cory, S. Oncogene Res. (in the press).
Mann, R., Mulligan, R. C. & Baltimore, D. Cell 33, 153–159 (1983).
Whitlock, C. A., Tidmarsh, G. F., Muller-Sieberg, C. & Weissmann, I. L. Cell 48, 1009–1021 (1987).
Cory, S., Bernard, O., Bowtell, D., Schrader, S. & Schrader, J. W. Oncogene Res. 1, 61–76 (1987).
Cook, W. D., Metcalf, D., Nicola, N. A., Burgess, A. W. & Walker, F. Cell 41, 677–683 (1985).
Metcalf, D., Roberts, T. M., Cherington, V. & Dunn, A. R. EMBO J. 6, 3703–3709 (1987).
Wheeler, E. F., Askew, D., Day, D., Ihle, J. N. & Sher, C. J. Molec. cell. Biol. 7, 1673–1680 (1987).
Whetton, A. D., Heyworth, C. M. & Dexter, T. M. J. Cell. Sci. 84, 93–104 (1986).
Whetton, A. D. & Dexter, T. M. Nature 303, 629–632 (1983).
Jaffe, E. S. J. natn. Cancer Inst. 70, 401–403 (1983).
Freitas, A. A., Rocha, B., Forni, L. & Coutinho, A. J. Immun. 128, 54–60 (1982).
Gauwerky C. E., Hoxie, J., Nowell, P. C. & Croce, C. M. Oncogene 2, 431–435 (1988).
Cepko, C. L., Roberts, B. E. & Mulligan, R. C. Cell 37, 1053–1062 (1984).
Bowtell, D. D. L., Johnson, G. R., Kelso, A. & Cory, S. Molec. biol. Med. 4, 229–250 (1987).
Korman, A., Frantz, D., Strominger, J. & Mulligan, R. C. Proc. natn. Acad. Sci. U.S.A. 84, 2150–2154 (1987).
Taylor, I. W. J. Histochem. Cytochem. 28, 1021–1024 (1980).
Dean, P. D. Cell Tissue Kinet. 13, 299–308 (1980).
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Vaux, D., Cory, S. & Adams, J. Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature 335, 440–442 (1988). https://doi.org/10.1038/335440a0
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DOI: https://doi.org/10.1038/335440a0
