Skip to main content
Cell Regulation logoLink to Cell Regulation
. 1991 Sep;2(9):699–708. doi: 10.1091/mbc.2.9.699

Selective expression of high molecular weight basic fibroblast growth factor confers a unique phenotype to NIH 3T3 cells.

N Quarto 1, D Talarico 1, R Florkiewicz 1, D B Rifkin 1
PMCID: PMC361864  PMID: 1660309

Abstract

The phenotypes of NIH 3T3 cells transfected with basic fibroblast growth factor (bFGF) cDNAs that express only the high molecular weight (HMW) forms of bFGF, the 18-kDa form, or all forms were examined. Cells producing the 18 kDa or all forms of bFGF were transformed at high levels of growth factor expression but were nontransformed at low levels. Cell producing low levels of HMW forms of bFGF were growth impaired when compared with the parental cells. These cells tended to form multinucleated giant cells, did not grow in soft agar, were nontumorigenic, had a normal bFGF receptor number, and had a nontransformed morphology. Cells expressing high levels of HMW bFGFs had a transformed morphology and were tumorigenic. These data suggest a specific functional role for HMWbFGF.

Full text

PDF
699

Images in this article

Selected References

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

  1. Abraham J. A., Mergia A., Whang J. L., Tumolo A., Friedman J., Hjerrild K. A., Gospodarowicz D., Fiddes J. C. Nucleotide sequence of a bovine clone encoding the angiogenic protein, basic fibroblast growth factor. Science. 1986 Aug 1;233(4763):545–548. doi: 10.1126/science.2425435. [DOI] [PubMed] [Google Scholar]
  2. Acland P., Dixon M., Peters G., Dickson C. Subcellular fate of the int-2 oncoprotein is determined by choice of initiation codon. Nature. 1990 Feb 15;343(6259):662–665. doi: 10.1038/343662a0. [DOI] [PubMed] [Google Scholar]
  3. Boffa L. C., Karn J., Vidali G., Allfrey V. G. Distribution of NG, NG,-dimethylarginine in nuclear protein fractions. Biochem Biophys Res Commun. 1977 Feb 7;74(3):969–976. doi: 10.1016/0006-291x(77)91613-8. [DOI] [PubMed] [Google Scholar]
  4. Burgess W. H., Bizik J., Mehlman T., Quarto N., Rifkin D. B. Direct evidence for methylation of arginine residues in high molecular weight forms of basic fibroblast growth factor. Cell Regul. 1991 Feb;2(2):87–93. doi: 10.1091/mbc.2.2.87. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Burgess W. H., Maciag T. The heparin-binding (fibroblast) growth factor family of proteins. Annu Rev Biochem. 1989;58:575–606. doi: 10.1146/annurev.bi.58.070189.003043. [DOI] [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. Christensen M. E., Beyer A. L., Walker B., Lestourgeon W. M. Identification of NG, NG-dimethylarginine in a nuclear protein from the lower eukaryote physarum polycephalum homologous to the major proteins of mammalian 40S ribonucleoprotein particles. Biochem Biophys Res Commun. 1977 Jan 24;74(2):621–629. doi: 10.1016/0006-291x(77)90348-5. [DOI] [PubMed] [Google Scholar]
  8. Esch F., Baird A., Ling N., Ueno N., Hill F., Denoroy L., Klepper R., Gospodarowicz D., Böhlen P., Guillemin R. Primary structure of bovine pituitary basic fibroblast growth factor (FGF) and comparison with the amino-terminal sequence of bovine brain acidic FGF. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6507–6511. doi: 10.1073/pnas.82.19.6507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Florkiewicz R. Z., Sommer A. Human basic fibroblast growth factor gene encodes four polypeptides: three initiate translation from non-AUG codons. Proc Natl Acad Sci U S A. 1989 Jun;86(11):3978–3981. doi: 10.1073/pnas.86.11.3978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hann S. R., King M. W., Bentley D. L., Anderson C. W., Eisenman R. N. A non-AUG translational initiation in c-myc exon 1 generates an N-terminally distinct protein whose synthesis is disrupted in Burkitt's lymphomas. Cell. 1988 Jan 29;52(2):185–195. doi: 10.1016/0092-8674(88)90507-7. [DOI] [PubMed] [Google Scholar]
  11. Joseph-Silverstein J., Moscatelli D., Rifkin D. B. The development of a quantitative RIA for basic fibroblast growth factor using polyclonal antibodies against the 157 amino acid form of human bFGF. The identification of bFGF in adherent elicited murine peritoneal macrophages. J Immunol Methods. 1988 Jun 13;110(2):183–192. doi: 10.1016/0022-1759(88)90102-0. [DOI] [PubMed] [Google Scholar]
  12. Kaufmann S. H., Coffey D. S., Shaper J. H. Considerations in the isolation of rat liver nuclear matrix, nuclear envelope, and pore complex lamina. Exp Cell Res. 1981 Mar;132(1):105–123. doi: 10.1016/0014-4827(81)90088-4. [DOI] [PubMed] [Google Scholar]
  13. Machamer C. E., Florkiewicz R. Z., Rose J. K. A single N-linked oligosaccharide at either of the two normal sites is sufficient for transport of vesicular stomatitis virus G protein to the cell surface. Mol Cell Biol. 1985 Nov;5(11):3074–3083. doi: 10.1128/mcb.5.11.3074. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Moscatelli D., Joseph-Silverstein J., Manejias R., Rifkin D. B. Mr 25,000 heparin-binding protein from guinea pig brain is a high molecular weight form of basic fibroblast growth factor. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5778–5782. doi: 10.1073/pnas.84.16.5778. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Moscatelli D., Presta M., Rifkin D. B. Purification of a factor from human placenta that stimulates capillary endothelial cell protease production, DNA synthesis, and migration. Proc Natl Acad Sci U S A. 1986 Apr;83(7):2091–2095. doi: 10.1073/pnas.83.7.2091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Moscatelli D., Quarto N. Transformation of NIH 3T3 cells with basic fibroblast growth factor or the hst/K-fgf oncogene causes downregulation of the fibroblast growth factor receptor: reversal of morphological transformation and restoration of receptor number by suramin. J Cell Biol. 1989 Nov;109(5):2519–2527. doi: 10.1083/jcb.109.5.2519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Prats H., Kaghad M., Prats A. C., Klagsbrun M., Lélias J. M., Liauzun P., Chalon P., Tauber J. P., Amalric F., Smith J. A. High molecular mass forms of basic fibroblast growth factor are initiated by alternative CUG codons. Proc Natl Acad Sci U S A. 1989 Mar;86(6):1836–1840. doi: 10.1073/pnas.86.6.1836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Quarto N., Talarico D., Sommer A., Florkiewicz R., Basilico C., Rifkin D. B. Transformation by basic fibroblast growth factor requires high levels of expression: comparison with transformation by hst/K-fgf. Oncogene Res. 1989;5(2):101–110. [PubMed] [Google Scholar]
  19. Renko M., Quarto N., Morimoto T., Rifkin D. B. Nuclear and cytoplasmic localization of different basic fibroblast growth factor species. J Cell Physiol. 1990 Jul;144(1):108–114. doi: 10.1002/jcp.1041440114. [DOI] [PubMed] [Google Scholar]
  20. Rifkin D. B., Moscatelli D. Recent developments in the cell biology of basic fibroblast growth factor. J Cell Biol. 1989 Jul;109(1):1–6. doi: 10.1083/jcb.109.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sommer A., Brewer M. T., Thompson R. C., Moscatelli D., Presta M., Rifkin D. B. A form of human basic fibroblast growth factor with an extended amino terminus. Biochem Biophys Res Commun. 1987 Apr 29;144(2):543–550. doi: 10.1016/s0006-291x(87)80001-3. [DOI] [PubMed] [Google Scholar]

Articles from Cell Regulation are provided here courtesy of American Society for Cell Biology

RESOURCES