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. 1989 Dec;9(12):5746–5749. doi: 10.1128/mcb.9.12.5746

Rates of mutation to growth factor autonomy and tumorigenicity differ in hematopoietic stem and precursor cells expressing the multilineage colony-stimulating factor gene.

C Laker 1, N Kluge 1, C Stocking 1, U Just 1, M J Franz 1, W Ostertag 1, J F DeLamarter 1, M Dexter 1, E Spooncer 1
PMCID: PMC363750  PMID: 2586530

Abstract

At least two separate but interdependent events are required to attain autonomous growth as a consequence of ectopic expression of the multilineage colony-stimulating factor gene in hematopoietic progenitor cells. The rate at which the second event occurs is more than 3 orders of magnitude higher in precursor cell lines (FDC-P1 or FDC-P2) than in stem cell lines (FDC-Pmix). Autonomous, but not density-dependent, growth is tightly coupled to tumorigenicity in precursor cells; however, neither growth-factor-independent nor autonomously growing stem cell lines are tumorigenic.

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Selected References

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

  1. Browder T. M., Abrams J. S., Wong P. M., Nienhuis A. W. Mechanism of autocrine stimulation in hematopoietic cells producing interleukin-3 after retrovirus-mediated gene transfer. Mol Cell Biol. 1989 Jan;9(1):204–213. doi: 10.1128/mcb.9.1.204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Colbère-Garapin F., Horodniceanu F., Kourilsky P., Garapin A. C. A new dominant hybrid selective marker for higher eukaryotic cells. J Mol Biol. 1981 Jul 25;150(1):1–14. doi: 10.1016/0022-2836(81)90321-1. [DOI] [PubMed] [Google Scholar]
  3. Dexter T. M., Garland J., Scott D., Scolnick E., Metcalf D. Growth of factor-dependent hemopoietic precursor cell lines. J Exp Med. 1980 Oct 1;152(4):1036–1047. doi: 10.1084/jem.152.4.1036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Haeuptle M. T., Flint N., Gough N. M., Dobberstein B. A tripartite structure of the signals that determine protein insertion into the endoplasmic reticulum membrane. J Cell Biol. 1989 Apr;108(4):1227–1236. doi: 10.1083/jcb.108.4.1227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hapel A. J., Vande Woude G., Campbell H. D., Young I. G., Robins T. Generation of an autocrine leukaemia using a retroviral expression vector carrying the interleukin-3 gene. Lymphokine Res. 1986 Fall;5(4):249–254. [PubMed] [Google Scholar]
  6. Heldin C. H., Betsholtz C., Claesson-Welsh L., Westermark B. Subversion of growth regulatory pathways in malignant transformation. Biochim Biophys Acta. 1987 Nov 25;907(3):219–244. doi: 10.1016/0304-419x(87)90007-2. [DOI] [PubMed] [Google Scholar]
  7. Keating M. T., Williams L. T. Autocrine stimulation of intracellular PDGF receptors in v-sis-transformed cells. Science. 1988 Feb 19;239(4842):914–916. doi: 10.1126/science.2829358. [DOI] [PubMed] [Google Scholar]
  8. Laker C., Stocking C., Bergholz U., Hess N., De Lamarter J. F., Ostertag W. Autocrine stimulation after transfer of the granulocyte/macrophage colony-stimulating factor gene and autonomous growth are distinct but interdependent steps in the oncogenic pathway. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8458–8462. doi: 10.1073/pnas.84.23.8458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Lang R. A., Metcalf D., Gough N. M., Dunn A. R., Gonda T. J. Expression of a hemopoietic growth factor cDNA in a factor-dependent cell line results in autonomous growth and tumorigenicity. Cell. 1985 Dec;43(2 Pt 1):531–542. doi: 10.1016/0092-8674(85)90182-5. [DOI] [PubMed] [Google Scholar]
  10. Metcalf D. The granulocyte-macrophage colony-stimulating factors. Science. 1985 Jul 5;229(4708):16–22. doi: 10.1126/science.2990035. [DOI] [PubMed] [Google Scholar]
  11. Ostertag W., Stocking C., Johnson G. R., Kluge N., Kollek R., Franz T., Hess N. Transforming genes and target cells of murine spleen focus-forming viruses. Adv Cancer Res. 1987;48:193–355. doi: 10.1016/s0065-230x(08)60693-4. [DOI] [PubMed] [Google Scholar]
  12. Schrader J. W., Crapper R. M. Autogenous production of a hemopoietic growth factor, persisting-cell-stimulating factor, as a mechanism for transformation of bone marrow-derived cells. Proc Natl Acad Sci U S A. 1983 Nov;80(22):6892–6896. doi: 10.1073/pnas.80.22.6892. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Spooncer E., Heyworth C. M., Dunn A., Dexter T. M. Self-renewal and differentiation of interleukin-3-dependent multipotent stem cells are modulated by stromal cells and serum factors. Differentiation. 1986;31(2):111–118. doi: 10.1111/j.1432-0436.1986.tb00391.x. [DOI] [PubMed] [Google Scholar]
  14. Stocking C., Kollek R., Bergholz U., Ostertag W. Long terminal repeat sequences impart hematopoietic transformation properties to the myeloproliferative sarcoma virus. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5746–5750. doi: 10.1073/pnas.82.17.5746. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Stocking C., Löliger C., Kawai M., Suciu S., Gough N., Ostertag W. Identification of genes involved in growth autonomy of hematopoietic cells by analysis of factor-independent mutants. Cell. 1988 Jun 17;53(6):869–879. doi: 10.1016/s0092-8674(88)90329-7. [DOI] [PubMed] [Google Scholar]
  16. Wong P. M., Chung S. W., Nienhuis A. W. Retroviral transfer and expression of the interleukin-3 gene in hemopoietic cells. Genes Dev. 1987 Jun;1(4):358–365. doi: 10.1101/gad.1.4.358. [DOI] [PubMed] [Google Scholar]

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