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. 1988 Feb;8(2):588–594. doi: 10.1128/mcb.8.2.588

Transformation of mouse BALB/c 3T3 cells with human basic fibroblast growth factor cDNA.

R Sasada 1, T Kurokawa 1, M Iwane 1, K Igarashi 1
PMCID: PMC363184  PMID: 2832728

Abstract

The expression of human basic fibroblast growth factor (bFGF) cDNA in mouse BALB/c 3T3 clone A31 cells induced morphological transformation. These transformed cells grew well and reached more than a sixfold-higher saturation density than parental A31 cells even in serum-free medium. They were able to form colonies in soft agar. The phenotypic alteration in the transformed cells was reversed by the addition of anti-human bFGF antibodies to the medium. These results suggest that the cellular transformation mediated by bFGF is caused by autocrine stimulation with secreted bFGF molecules.

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Selected References

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  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. Abraham J. A., Whang J. L., Tumolo A., Mergia A., Friedman J., Gospodarowicz D., Fiddes J. C. Human basic fibroblast growth factor: nucleotide sequence and genomic organization. EMBO J. 1986 Oct;5(10):2523–2528. doi: 10.1002/j.1460-2075.1986.tb04530.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baird A., Esch F., Mormède P., Ueno N., Ling N., Böhlen P., Ying S. Y., Wehrenberg W. B., Guillemin R. Molecular characterization of fibroblast growth factor: distribution and biological activities in various tissues. Recent Prog Horm Res. 1986;42:143–205. doi: 10.1016/b978-0-12-571142-5.50008-2. [DOI] [PubMed] [Google Scholar]
  4. Betsholtz C., Westermark B., Ek B., Heldin C. H. Coexpression of a PDGF-like growth factor and PDGF receptors in a human osteosarcoma cell line: implications for autocrine receptor activation. Cell. 1984 Dec;39(3 Pt 2):447–457. doi: 10.1016/0092-8674(84)90452-5. [DOI] [PubMed] [Google Scholar]
  5. Bottenstein J., Hayashi I., Hutchings S., Masui H., Mather J., McClure D. B., Ohasa S., Rizzino A., Sato G., Serrero G. The growth of cells in serum-free hormone-supplemented media. Methods Enzymol. 1979;58:94–109. doi: 10.1016/s0076-6879(79)58127-0. [DOI] [PubMed] [Google Scholar]
  6. Brinster R. L., Chen H. Y., Trumbauer M., Senear A. W., Warren R., Palmiter R. D. Somatic expression of herpes thymidine kinase in mice following injection of a fusion gene into eggs. Cell. 1981 Nov;27(1 Pt 2):223–231. doi: 10.1016/0092-8674(81)90376-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  8. Cuttitta F., Carney D. N., Mulshine J., Moody T. W., Fedorko J., Fischler A., Minna J. D. Bombesin-like peptides can function as autocrine growth factors in human small-cell lung cancer. 1985 Aug 29-Sep 4Nature. 316(6031):823–826. doi: 10.1038/316823a0. [DOI] [PubMed] [Google Scholar]
  9. Davis B. D., Tai P. C. The mechanism of protein secretion across membranes. Nature. 1980 Jan 31;283(5746):433–438. doi: 10.1038/283433a0. [DOI] [PubMed] [Google Scholar]
  10. Folkman J., Klagsbrun M. Angiogenic factors. Science. 1987 Jan 23;235(4787):442–447. doi: 10.1126/science.2432664. [DOI] [PubMed] [Google Scholar]
  11. Gazit A., Igarashi H., Chiu I. M., Srinivasan A., Yaniv A., Tronick S. R., Robbins K. C., Aaronson S. A. Expression of the normal human sis/PDGF-2 coding sequence induces cellular transformation. Cell. 1984 Nov;39(1):89–97. doi: 10.1016/0092-8674(84)90194-6. [DOI] [PubMed] [Google Scholar]
  12. Gill G. N., Lazar C. S. Increased phosphotyrosine content and inhibition of proliferation in EGF-treated A431 cells. Nature. 1981 Sep 24;293(5830):305–307. doi: 10.1038/293305a0. [DOI] [PubMed] [Google Scholar]
  13. Gospodarowicz D., Moran J. S. Growth factors in mammalian cell culture. Annu Rev Biochem. 1976;45:531–558. doi: 10.1146/annurev.bi.45.070176.002531. [DOI] [PubMed] [Google Scholar]
  14. Gospodarowicz D., Moran J. S. Stimulation of division of sparse and confluent 3T3 cell populations by a fibroblast growth factor, dexamethasone, and insulin. Proc Natl Acad Sci U S A. 1974 Nov;71(11):4584–4588. doi: 10.1073/pnas.71.11.4584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gospodarowicz D., Moran J. Effect of a fibroblast growth factor, insulin, dexamethasone, and serum on the morphology of BALB/c 3T3 cells. Proc Natl Acad Sci U S A. 1974 Dec;71(12):4648–4652. doi: 10.1073/pnas.71.12.4648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gospodarowicz D., Neufeld G., Schweigerer L. Fibroblast growth factor. Mol Cell Endocrinol. 1986 Aug;46(3):187–204. doi: 10.1016/0303-7207(86)90001-8. [DOI] [PubMed] [Google Scholar]
  17. Hamer D. H. Metallothionein. Annu Rev Biochem. 1986;55:913–951. doi: 10.1146/annurev.bi.55.070186.004405. [DOI] [PubMed] [Google Scholar]
  18. Heldin C. H., Westermark B. Growth factors: mechanism of action and relation to oncogenes. Cell. 1984 May;37(1):9–20. doi: 10.1016/0092-8674(84)90296-4. [DOI] [PubMed] [Google Scholar]
  19. Huang J. S., Huang S. S., Deuel T. F. Transforming protein of simian sarcoma virus stimulates autocrine growth of SSV-transformed cells through PDGF cell-surface receptors. Cell. 1984 Nov;39(1):79–87. doi: 10.1016/0092-8674(84)90193-4. [DOI] [PubMed] [Google Scholar]
  20. Iwane M., Kurokawa T., Sasada R., Seno M., Nakagawa S., Igarashi K. Expression of cDNA encoding human basic fibroblast growth factor in E. coli. Biochem Biophys Res Commun. 1987 Jul 31;146(2):470–477. doi: 10.1016/0006-291x(87)90553-5. [DOI] [PubMed] [Google Scholar]
  21. Johnsson A., Betsholtz C., Heldin C. H., Westermark B. Antibodies against platelet-derived growth factor inhibit acute transformation by simian sarcoma virus. Nature. 1985 Oct 3;317(6036):438–440. doi: 10.1038/317438a0. [DOI] [PubMed] [Google Scholar]
  22. Kakunaga T., Crow J. D. Cell variants showing differential susceptibility to ultraviolet light--induced transformation. Science. 1980 Jul 25;209(4455):505–507. doi: 10.1126/science.7394516. [DOI] [PubMed] [Google Scholar]
  23. Kurokawa T., Sasada R., Iwane M., Igarashi K. Cloning and expression of cDNA encoding human basic fibroblast growth factor. FEBS Lett. 1987 Mar 9;213(1):189–194. doi: 10.1016/0014-5793(87)81489-8. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Lee W., Haslinger A., Karin M., Tjian R. Activation of transcription by two factors that bind promoter and enhancer sequences of the human metallothionein gene and SV40. Nature. 1987 Jan 22;325(6102):368–372. doi: 10.1038/325368a0. [DOI] [PubMed] [Google Scholar]
  26. Lehrach H., Diamond D., Wozney J. M., Boedtker H. RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination. Biochemistry. 1977 Oct 18;16(21):4743–4751. doi: 10.1021/bi00640a033. [DOI] [PubMed] [Google Scholar]
  27. Neufeld G., Gospodarowicz D. Basic and acidic fibroblast growth factors interact with the same cell surface receptors. J Biol Chem. 1986 Apr 25;261(12):5631–5637. [PubMed] [Google Scholar]
  28. Okayama H., Berg P. A cDNA cloning vector that permits expression of cDNA inserts in mammalian cells. Mol Cell Biol. 1983 Feb;3(2):280–289. doi: 10.1128/mcb.3.2.280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Ozanne B., Fulton R. J., Kaplan P. L. Kirsten murine sarcoma virus transformed cell lines and a spontaneously transformed rat cell-line produce transforming factors. J Cell Physiol. 1980 Oct;105(1):163–180. doi: 10.1002/jcp.1041050118. [DOI] [PubMed] [Google Scholar]
  30. Robbins K. C., Leal F., Pierce J. H., Aaronson S. A. The v-sis/PDGF-2 transforming gene product localizes to cell membranes but is not a secretory protein. EMBO J. 1985 Jul;4(7):1783–1792. doi: 10.1002/j.1460-2075.1985.tb03851.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Rosenthal A., Lindquist P. B., Bringman T. S., Goeddel D. V., Derynck R. Expression in rat fibroblasts of a human transforming growth factor-alpha cDNA results in transformation. Cell. 1986 Jul 18;46(2):301–309. doi: 10.1016/0092-8674(86)90747-6. [DOI] [PubMed] [Google Scholar]
  32. Sasada R., Onda H., Igarashi K. The establishment of IL-2 producing cells by genetic engineering. Cell Struct Funct. 1987 Apr;12(2):205–217. doi: 10.1247/csf.12.205. [DOI] [PubMed] [Google Scholar]
  33. Serfling E., Lübbe A., Dorsch-Häsler K., Schaffner W. Metal-dependent SV40 viruses containing inducible enhancers from the upstream region of metallothionein genes. EMBO J. 1985 Dec 30;4(13B):3851–3859. doi: 10.1002/j.1460-2075.1985.tb04157.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sporn M. B., Roberts A. B. Autocrine growth factors and cancer. 1985 Feb 28-Mar 6Nature. 313(6005):745–747. doi: 10.1038/313745a0. [DOI] [PubMed] [Google Scholar]
  35. Sporn M. B., Todaro G. J. Autocrine secretion and malignant transformation of cells. N Engl J Med. 1980 Oct 9;303(15):878–880. doi: 10.1056/NEJM198010093031511. [DOI] [PubMed] [Google Scholar]
  36. Stern D. F., Hare D. L., Cecchini M. A., Weinberg R. A. Construction of a novel oncogene based on synthetic sequences encoding epidermal growth factor. Science. 1987 Jan 16;235(4786):321–324. doi: 10.1126/science.3492043. [DOI] [PubMed] [Google Scholar]
  37. Waterfield M. D., Scrace G. T., Whittle N., Stroobant P., Johnsson A., Wasteson A., Westermark B., Heldin C. H., Huang J. S., Deuel T. F. Platelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus. Nature. 1983 Jul 7;304(5921):35–39. doi: 10.1038/304035a0. [DOI] [PubMed] [Google Scholar]
  38. Wigler M., Sweet R., Sim G. K., Wold B., Pellicer A., Lacy E., Maniatis T., Silverstein S., Axel R. Transformation of mammalian cells with genes from procaryotes and eucaryotes. Cell. 1979 Apr;16(4):777–785. doi: 10.1016/0092-8674(79)90093-x. [DOI] [PubMed] [Google Scholar]
  39. de Larco J. E., Todaro G. J. Growth factors from murine sarcoma virus-transformed cells. Proc Natl Acad Sci U S A. 1978 Aug;75(8):4001–4005. doi: 10.1073/pnas.75.8.4001. [DOI] [PMC free article] [PubMed] [Google Scholar]

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