Skip to main content
PMC home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1987 May;7(5):1673–1680. doi: 10.1128/mcb.7.5.1673

The v-fms oncogene induces factor-independent growth and transformation of the interleukin-3-dependent myeloid cell line FDC-P1.

E F Wheeler, D Askew, S May, J N Ihle, C J Sherr
PMCID: PMC365267  PMID: 3037331

Abstract

The normal cellular counterpart of the v-fms oncogene product is a receptor for the mononuclear phagocyte colony-stimulating factor, CSF-1. An interleukin-3 (IL-3)-dependent mouse myeloid cell line, FDC-P1, was infected with a murine retrovirus vector containing v-fms linked to a gene encoding resistance to neomycin (neo). Infected cells selected for resistance to the aminoglycoside G418 contained few proviral DNA copies per haploid genome, expressed low levels of the v-fms-coded glycoprotein, remained IL-3 dependent for growth, and were nontumorigenic in nude mice. In contrast, infected cells selected for their ability to grow in the absence of IL-3 contained an increased number of proviral insertions, expressed high levels of the v-fms-coded glycoprotein, and were tumorigenic in nude mice. The IL-3-independent cells expressed IL-3 receptors of comparable number and affinity to those detected in uninfected FDC-P1 cells and did not produce a growth factor able to support replication of the parental cells. Thus, the synthesis of high levels of the v-fms gene product in FDC-P1 cells abrogated their requirement for IL-3 and rendered the cells tumorigenic by a nonautocrine mechanism. The data suggest that v-fms encodes a promiscuous tyrosine kinase able to transform cells of the myeloid lineage that do not normally express CSF-1 receptors.

Full text

PDF
1673

Images in this article

1676Image
on p.1676
1676Image
on p.1676

Selected References

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

  1. Adkins B., Leutz A., Graf T. Autocrine growth induced by src-related oncogenes in transformed chicken myeloid cells. Cell. 1984 Dec;39(3 Pt 2):439–445. doi: 10.1016/0092-8674(84)90451-3. [DOI] [PubMed] [Google Scholar]
  2. Anderson S. J., Furth M., Wolff L., Ruscetti S. K., Sherr C. J. Monoclonal antibodies to the transformation-specific glycoprotein encoded by the feline retroviral oncogene v-fms. J Virol. 1982 Nov;44(2):696–702. doi: 10.1128/jvi.44.2.696-702.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Anderson S. J., Gonda M. A., Rettenmier C. W., Sherr C. J. Subcellular localization of glycoproteins encoded by the viral oncogene v-fms. J Virol. 1984 Sep;51(3):730–741. doi: 10.1128/jvi.51.3.730-741.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Anderson S. M., Klinken S. P., Hankins W. D. A murine recombinant retrovirus containing the src oncogene transforms erythroid precursor cells in vitro. Mol Cell Biol. 1985 Dec;5(12):3369–3375. doi: 10.1128/mcb.5.12.3369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Barbacid M., Lauver A. V. Gene products of McDonough feline sarcoma virus have an in vitro-associated protein kinase that phosphorylates tyrosine residues: lack of detection of this enzymatic activity in vivo. J Virol. 1981 Dec;40(3):812–821. doi: 10.1128/jvi.40.3.812-821.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cepko C. L., Roberts B. E., Mulligan R. C. Construction and applications of a highly transmissible murine retrovirus shuttle vector. Cell. 1984 Jul;37(3):1053–1062. doi: 10.1016/0092-8674(84)90440-9. [DOI] [PubMed] [Google Scholar]
  7. Cook W. D., Metcalf D., Nicola N. A., Burgess A. W., Walker F. Malignant transformation of a growth factor-dependent myeloid cell line by Abelson virus without evidence of an autocrine mechanism. Cell. 1985 Jul;41(3):677–683. doi: 10.1016/s0092-8674(85)80048-9. [DOI] [PubMed] [Google Scholar]
  8. Cooper J. A., Gould K. L., Cartwright C. A., Hunter T. Tyr527 is phosphorylated in pp60c-src: implications for regulation. Science. 1986 Mar 21;231(4744):1431–1434. doi: 10.1126/science.2420005. [DOI] [PubMed] [Google Scholar]
  9. Courtneidge S. A. Activation of the pp60c-src kinase by middle T antigen binding or by dephosphorylation. EMBO J. 1985 Jun;4(6):1471–1477. doi: 10.1002/j.1460-2075.1985.tb03805.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Coussens L., Van Beveren C., Smith D., Chen E., Mitchell R. L., Isacke C. M., Verma I. M., Ullrich A. Structural alteration of viral homologue of receptor proto-oncogene fms at carboxyl terminus. Nature. 1986 Mar 20;320(6059):277–280. doi: 10.1038/320277a0. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Donner L., Fedele L. A., Garon C. F., Anderson S. J., Sherr C. J. McDonough feline sarcoma virus: characterization of the molecularly cloned provirus and its feline oncogene (v-fms). J Virol. 1982 Feb;41(2):489–500. doi: 10.1128/jvi.41.2.489-500.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Emerman M., Temin H. M. Genes with promoters in retrovirus vectors can be independently suppressed by an epigenetic mechanism. Cell. 1984 Dec;39(3 Pt 2):449–467. [PubMed] [Google Scholar]
  14. Emerman M., Temin H. M. Quantitative analysis of gene suppression in integrated retrovirus vectors. Mol Cell Biol. 1986 Mar;6(3):792–800. doi: 10.1128/mcb.6.3.792. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Furman W. L., Rettenmier C. W., Chen J. H., Roussel M. F., Quinn C. O., Sherr C. J. Antibodies to distal carboxyl terminal epitopes in the v-fms-coded glycoprotein do not cross-react with the c-fms gene product. Virology. 1986 Jul 30;152(2):432–445. doi: 10.1016/0042-6822(86)90145-5. [DOI] [PubMed] [Google Scholar]
  16. Graf T., von Weizsaecker F., Grieser S., Coll J., Stehelin D., Patschinsky T., Bister K., Bechade C., Calothy G., Leutz A. v-mil induces autocrine growth and enhanced tumorigenicity in v-myc-transformed avian macrophages. Cell. 1986 May 9;45(3):357–364. doi: 10.1016/0092-8674(86)90321-1. [DOI] [PubMed] [Google Scholar]
  17. Graham F. L., van der Eb A. J. Transformation of rat cells by DNA of human adenovirus 5. Virology. 1973 Aug;54(2):536–539. doi: 10.1016/0042-6822(73)90163-3. [DOI] [PubMed] [Google Scholar]
  18. Griffin J. D., Löwenberg B. Clonogenic cells in acute myeloblastic leukemia. Blood. 1986 Dec;68(6):1185–1195. [PubMed] [Google Scholar]
  19. Gross-Bellard M., Oudet P., Chambon P. Isolation of high-molecular-weight DNA from mammalian cells. Eur J Biochem. 1973 Jul 2;36(1):32–38. doi: 10.1111/j.1432-1033.1973.tb02881.x. [DOI] [PubMed] [Google Scholar]
  20. Hampe A., Gobet M., Sherr C. J., Galibert F. Nucleotide sequence of the feline retroviral oncogene v-fms shows unexpected homology with oncogenes encoding tyrosine-specific protein kinases. Proc Natl Acad Sci U S A. 1984 Jan;81(1):85–89. doi: 10.1073/pnas.81.1.85. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Iba H., Cross F. R., Garber E. A., Hanafusa H. Low level of cellular protein phosphorylation by nontransforming overproduced p60c-src. Mol Cell Biol. 1985 May;5(5):1058–1066. doi: 10.1128/mcb.5.5.1058. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ihle J. N., Keller J., Henderson L., Klein F., Palaszynski E. Procedures for the purification of interleukin 3 to homogeneity. J Immunol. 1982 Dec;129(6):2431–2436. [PubMed] [Google Scholar]
  23. Ihle J. N., Morse H. C., 3rd, Keller J., Holmes K. L. Interleukin 3 dependent retrovirus induced lymphomas: loss of the ability to terminally differentiate in response to differentiation factors. Curr Top Microbiol Immunol. 1984;113:86–91. doi: 10.1007/978-3-642-69860-6_16. [DOI] [PubMed] [Google Scholar]
  24. Kahn P., Adkins B., Beug H., Graf T. src- and fps-containing avian sarcoma viruses transform chicken erythroid cells. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7122–7126. doi: 10.1073/pnas.81.22.7122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kahn P., Frykberg L., Brady C., Stanley I., Beug H., Vennström B., Graf T. v-erbA cooperates with sarcoma oncogenes in leukemic cell transformation. Cell. 1986 May 9;45(3):349–356. doi: 10.1016/0092-8674(86)90320-x. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Laudano A. P., Buchanan J. M. Phosphorylation of tyrosine in the carboxyl-terminal tryptic peptide of pp60c-src. Proc Natl Acad Sci U S A. 1986 Feb;83(4):892–896. doi: 10.1073/pnas.83.4.892. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Levy J. B., Iba H., Hanafusa H. Activation of the transforming potential of p60c-src by a single amino acid change. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4228–4232. doi: 10.1073/pnas.83.12.4228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Manger R., Najita L., Nichols E. J., Hakomori S., Rohrschneider L. Cell surface expression of the McDonough strain of feline sarcoma virus fms gene product (gp 140fms). Cell. 1984 Dec;39(2 Pt 1):327–337. doi: 10.1016/0092-8674(84)90011-4. [DOI] [PubMed] [Google Scholar]
  30. Mann R., Mulligan R. C., Baltimore D. Construction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus. Cell. 1983 May;33(1):153–159. doi: 10.1016/0092-8674(83)90344-6. [DOI] [PubMed] [Google Scholar]
  31. Mathey-Prevot B., Nabel G., Palacios R., Baltimore D. Abelson virus abrogation of interleukin-3 dependence in a lymphoid cell line. Mol Cell Biol. 1986 Nov;6(11):4133–4135. doi: 10.1128/mcb.6.11.4133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. May W. S., Ihle J. N. Affinity isolation of the interleukin-3 surface receptor. Biochem Biophys Res Commun. 1986 Mar 28;135(3):870–879. doi: 10.1016/0006-291x(86)91009-0. [DOI] [PubMed] [Google Scholar]
  33. McDonough S. K., Larsen S., Brodey R. S., Stock N. D., Hardy W. D., Jr A transmissible feline fibrosarcoma of viral origin. Cancer Res. 1971 Jul;31(7):953–956. [PubMed] [Google Scholar]
  34. Oliff A., Agranovsky O., McKinney M. D., Murty V. V., Bauchwitz R. Friend murine leukemia virus-immortalized myeloid cells are converted into tumorigenic cell lines by Abelson leukemia virus. Proc Natl Acad Sci U S A. 1985 May;82(10):3306–3310. doi: 10.1073/pnas.82.10.3306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Palacios R., Neri T., Brockhaus M. Monoclonal antibodies specific for interleukin 3-sensitive murine cells. J Exp Med. 1986 Feb 1;163(2):369–382. doi: 10.1084/jem.163.2.369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Park L. S., Friend D., Gillis S., Urdal D. L. Characterization of the cell surface receptor for a multi-lineage colony-stimulating factor (CSF-2 alpha). J Biol Chem. 1986 Jan 5;261(1):205–210. [PubMed] [Google Scholar]
  37. Pierce J. H., Aaronson S. A., Anderson S. M. Hematopoietic cell transformation by a murine recombinant retrovirus containing the src gene of Rous sarcoma virus. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2374–2378. doi: 10.1073/pnas.81.8.2374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Pierce J. H., Di Fiore P. P., Aaronson S. A., Potter M., Pumphrey J., Scott A., Ihle J. N. Neoplastic transformation of mast cells by Abelson-MuLV: abrogation of IL-3 dependence by a nonautocrine mechanism. Cell. 1985 Jul;41(3):685–693. doi: 10.1016/s0092-8674(85)80049-0. [DOI] [PubMed] [Google Scholar]
  39. Rapp U. R., Cleveland J. L., Brightman K., Scott A., Ihle J. N. Abrogation of IL-3 and IL-2 dependence by recombinant murine retroviruses expressing v-myc oncogenes. Nature. 1985 Oct 3;317(6036):434–438. doi: 10.1038/317434a0. [DOI] [PubMed] [Google Scholar]
  40. Rettenmier C. W., Roussel M. F., Quinn C. O., Kitchingman G. R., Look A. T., Sherr C. J. Transmembrane orientation of glycoproteins encoded by the v-fms oncogene. Cell. 1985 Apr;40(4):971–981. doi: 10.1016/0092-8674(85)90357-5. [DOI] [PubMed] [Google Scholar]
  41. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  42. Rosenberg N., Baltimore D. A quantitative assay for transformation of bone marrow cells by Abelson murine leukemia virus. J Exp Med. 1976 Jun 1;143(6):1453–1463. doi: 10.1084/jem.143.6.1453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Roussel M. F., Dull T. J., Rettenmier C. W., Ralph P., Ullrich A., Sherr C. J. Transforming potential of the c-fms proto-oncogene (CSF-1 receptor). Nature. 1987 Feb 5;325(6104):549–552. doi: 10.1038/325549a0. [DOI] [PubMed] [Google Scholar]
  44. Roussel M. F., Rettenmier C. W., Look A. T., Sherr C. J. Cell surface expression of v-fms-coded glycoproteins is required for transformation. Mol Cell Biol. 1984 Oct;4(10):1999–2009. doi: 10.1128/mcb.4.10.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Ruscetti S. K., Turek L. P., Sherr C. J. Three independent isolates of feline sarcoma virus code for three distinct gag-x polyproteins. J Virol. 1980 Jul;35(1):259–264. doi: 10.1128/jvi.35.1.259-264.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Sarma P. S., Sharar A. L., McDonough S. The SM strain of feline sarcoma virus. Biologic and antigenic characterization of virus. Proc Soc Exp Biol Med. 1972 Sep;140(4):1365–1368. doi: 10.3181/00379727-140-36675. [DOI] [PubMed] [Google Scholar]
  47. Schwarzbaum S., Halpern R., Diamond B. The generation of macrophage-like cell lines by transfection with SV40 origin defective DNA. J Immunol. 1984 Mar;132(3):1158–1162. [PubMed] [Google Scholar]
  48. Sherr C. J., Rettenmier C. W., Sacca R., Roussel M. F., Look A. T., Stanley E. R. The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1. Cell. 1985 Jul;41(3):665–676. doi: 10.1016/s0092-8674(85)80047-7. [DOI] [PubMed] [Google Scholar]
  49. Sorensen P., Farber N. M., Krystal G. Identification of the interleukin-3 receptor using an iodinatable, cleavable, photoreactive cross-linking agent. J Biol Chem. 1986 Jul 15;261(20):9094–9097. [PubMed] [Google Scholar]
  50. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  51. Takeya T., Feldman R. A., Hanafusa H. DNA sequence of the viral and cellular src gene of chickens. 1. Complete nucleotide sequence of an EcoRI fragment of recovered avian sarcoma virus which codes for gp37 and pp60src. J Virol. 1982 Oct;44(1):1–11. doi: 10.1128/jvi.44.1.1-11.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Walker F., Nicola N. A., Metcalf D., Burgess A. W. Hierarchical down-modulation of hemopoietic growth factor receptors. Cell. 1985 Nov;43(1):269–276. doi: 10.1016/0092-8674(85)90032-7. [DOI] [PubMed] [Google Scholar]
  53. Wheeler E. F., Rettenmier C. W., Look A. T., Sherr C. J. The v-fms oncogene induces factor independence and tumorigenicity in CSF-1 dependent macrophage cell line. 1986 Nov 27-Dec 3Nature. 324(6095):377–380. doi: 10.1038/324377a0. [DOI] [PubMed] [Google Scholar]
  54. Wheeler E. F., Roussel M. F., Hampe A., Walker M. H., Fried V. A., Look A. T., Rettenmier C. W., Sherr C. J. The amino-terminal domain of the v-fms oncogene product includes a functional signal peptide that directs synthesis of a transforming glycoprotein in the absence of feline leukemia virus gag sequences. J Virol. 1986 Aug;59(2):224–233. doi: 10.1128/jvi.59.2.224-233.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES