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. 1987 Oct;7(10):3380–3385. doi: 10.1128/mcb.7.10.3380

A factor present in fetal calf serum enhances oncogene-induced transformation of rodent fibroblasts.

W L Hsiao 1, C A Lopez 1, T Wu 1, I B Weinstein 1
PMCID: PMC367987  PMID: 3316975

Abstract

Our previous studies indicated that addition of the tumor promoters 12-O-tetradecanoylphorbol-13-acetate (TPA) or teleocidin to Dulbecco modified Eagle medium supplemented with calf serum enhanced T24-induced focus formation in both the murine C3H 10T1/2 and rat 6 embryo fibroblast cell lines. In the present studies we have found that fetal calf serum (FCS) is more potent than 12-O-tetradecanoylphorbol-13-acetate in enhancing T24-induced focus formation, in terms of the number and size of the foci, in both C3H 10T1/2 and rat 6 cells. Time course studies indicate that FCS can exert this enhancing effect when it is added several days after the transfection with T24 DNA. In rat 6 cells, an 11-fold increase in T24-induced focus formation occurred when the transfected cultures were maintained for only 1 day in 5% FCS, starting 4 days after the transfection. Several known growth factors, including epidermal growth factor, transforming growth factors alpha and beta, insulin, and platelet-derived growth factor, did not enhance T24-induced transformation in these cell systems. Fractionation studies indicate that the factor present in FCS has a molecular weight of about 1,300, is not lipid soluble, and is acid, base, and heat stable. These findings suggest that a factor(s) normally present in serum may enhance the emergence of tumor cells in vivo, by acting in concert with an activated oncogene, during the multistage carcinogenic process.

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Selected References

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

  1. Bacchetti S., Graham F. L. Transfer of the gene for thymidine kinase to thymidine kinase-deficient human cells by purified herpes simplex viral DNA. Proc Natl Acad Sci U S A. 1977 Apr;74(4):1590–1594. doi: 10.1073/pnas.74.4.1590. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Backer J. M., Weinstein I. B. p21 ras proteins and guanine nucleotides modulate the phosphorylation of 36- and 17-kilodalton mitochondria-associated proteins. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6357–6361. doi: 10.1073/pnas.83.17.6357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Castagna M., Takai Y., Kaibuchi K., Sano K., Kikkawa U., Nishizuka Y. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem. 1982 Jul 10;257(13):7847–7851. [PubMed] [Google Scholar]
  4. 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]
  5. Dotto G. P., Parada L. F., Weinberg R. A. Specific growth response of ras-transformed embryo fibroblasts to tumour promoters. Nature. 1985 Dec 5;318(6045):472–475. doi: 10.1038/318472a0. [DOI] [PubMed] [Google Scholar]
  6. Fleischman L. F., Chahwala S. B., Cantley L. ras-transformed cells: altered levels of phosphatidylinositol-4,5-bisphosphate and catabolites. Science. 1986 Jan 24;231(4736):407–410. doi: 10.1126/science.3001936. [DOI] [PubMed] [Google Scholar]
  7. Freeman A. E., Price P. J., Igel H. J., Young J. C., Maryak J. M., Huebner R. J. Morphological transformation of rat embryo cells induced by diethylnitrosamine and murine leukemia viruses. J Natl Cancer Inst. 1970 Jan;44(1):65–78. [PubMed] [Google Scholar]
  8. Gattoni S., Kirschmeier P., Weinstein I. B., Escobedo J., Dina D. Cellular Moloney murine sarcoma (c-mos) sequences are hypermethylated and transcriptionally silent in normal and transformed rodent cells. Mol Cell Biol. 1982 Jan;2(1):42–51. doi: 10.1128/mcb.2.1.42. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Goldfarb M., Shimizu K., Perucho M., Wigler M. Isolation and preliminary characterization of a human transforming gene from T24 bladder carcinoma cells. Nature. 1982 Apr 1;296(5856):404–409. doi: 10.1038/296404a0. [DOI] [PubMed] [Google Scholar]
  10. Goustin A. S., Leof E. B., Shipley G. D., Moses H. L. Growth factors and cancer. Cancer Res. 1986 Mar;46(3):1015–1029. [PubMed] [Google Scholar]
  11. Hsiao W. L., Gattoni-Celli S., Weinstein I. B. Oncogene-induced transformation of C3H 10T1/2 cells is enhanced by tumor promoters. Science. 1984 Nov 2;226(4674):552–555. doi: 10.1126/science.6436974. [DOI] [PubMed] [Google Scholar]
  12. Hsiao W. L., Wu T., Weinstein I. B. Oncogene-induced transformation of a rat embryo fibroblast cell line is enhanced by tumor promoters. Mol Cell Biol. 1986 Jun;6(6):1943–1950. doi: 10.1128/mcb.6.6.1943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Land H., Parada L. F., Weinberg R. A. Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature. 1983 Aug 18;304(5927):596–602. doi: 10.1038/304596a0. [DOI] [PubMed] [Google Scholar]
  14. Mulligan R. C., Berg P. Selection for animal cells that express the Escherichia coli gene coding for xanthine-guanine phosphoribosyltransferase. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2072–2076. doi: 10.1073/pnas.78.4.2072. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Powers S., Kataoka T., Fasano O., Goldfarb M., Strathern J., Broach J., Wigler M. Genes in S. cerevisiae encoding proteins with domains homologous to the mammalian ras proteins. Cell. 1984 Mar;36(3):607–612. doi: 10.1016/0092-8674(84)90340-4. [DOI] [PubMed] [Google Scholar]
  16. Reznikoff C. A., Brankow D. W., Heidelberger C. Establishment and characterization of a cloned line of C3H mouse embryo cells sensitive to postconfluence inhibition of division. Cancer Res. 1973 Dec;33(12):3231–3238. [PubMed] [Google Scholar]

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