Skip to main content
Log in

Effects of retinoic acid on NIH3T3 cell transformation by the H-ras oncogene

  • Original Papers
  • Experimental Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Summary

Exposure of NIH3T3 cells to retinoic acid resulted in a dose-dependent modulation of transformed focus formation after transfection with an activated H-ras oncogene. Inhibition induced by 10 μM retinoic acid was maximal at 21.4% of control values. Maximal inhibition of transformation was found after exposure to 10 μM retinoic acid between days 0 and 3 of the transfection period. This concentration was also inhibitory for colony formation upon transfection of the non-transforming geneaph, suggesting that retinoic acid acts primarily on the process of transfection to inhibit focus or colony formation. Exposure to retinoic acid during the late period of the transfection protocol (days 14–20) resulted in alterations in focus morphology. A transformed cell line containing H-ras underwent reversion of the transformed phenotype after 4 weeks of treatment with retinoic acid, as determined by alterations in cell morphology and anchorage-independent growth. Phenotypic reversion was not associated with changes in the expression of the exogenous H-ras or endogenous c-myc or c-fos oncogenes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

DMEM:

Dulbecco's modified Eagle medium

SSC:

saline sodium citrate

TGF:

transforming growth factor

References

  • Anzano MA, Roberts AB, De Larco JE, Wakefield LM, Assoian RK, Roche NS, Smith JM, Sporn MB (1985) Increased secretion of type beta transforming growth factor accompanies viral transformation of cells. Mol Cell Biol 5:242–247

    Google Scholar 

  • Fitzgerald DJ, Barrett JC, Nettesheim P (1986) Changing responsiveness to all-trans retinoic acid of rat tracheal epithelial cells at different stages of neoplastic transformation. Carcinogenesis 7:1715–1721

    Google Scholar 

  • Garte SJ, Currie D, Troll W (1987) Inhibition of H-ras oncogene transformation of NIH3T3 cells by protease inhibitors. Cancer Res 47:3159–3162

    Google Scholar 

  • Garte SJ, Currie D, Motz J, Troll W (1988) Retinoic acid inhibits transformation of NIH3T3 cells by the human H-ras oncogene. Proc Am Assoc Cancer Res 29:140

    Google Scholar 

  • Giese NA, Neary KE, Levine N, Duffy JJ (1985) Inhibition by retinoic acid of murine retrovirus-induced cellular transformation and tumor formation. J Natl Cancer Inst 74:1135–1144

    Google Scholar 

  • Goodman DS (1984) Vitamin A and retinoids in health and disease. N Engl J Med 310:1023–1031

    Google Scholar 

  • Green S, Chambon P (1988) Nuclear receptors enhance our understanding of transcription regulation. Trends Genet 4:309–314

    Google Scholar 

  • Hossain MZ, Wilkens LR, Mehta PP, Bertram JS (1989) Enhancement of gap junctional communication by retinoids correlates with their ability to inhibit neoplastic transformation. Carcinogenesis 10:1743–1748

    Google Scholar 

  • Huang M, Kamata N, Nose K, Kuroki T (1988) Modified responsiveness of v-Ha-ras-transfected rat fibroblasts to growth factors and a tumor promoter. Mol Carcinogen 1:109–115

    Google Scholar 

  • Imaizumi M, Breitman TR (1988) Changes in c-myc, c-fms, and N-ras proto-oncogene expression associated with retinoic acid-induced monocytic differentiation of human leukemia HL60/MRI cells. Cancer Res 48:6733–6738

    Google Scholar 

  • Jetten AM, Barrett JC, Gilmer TM (1986) Differential response to retinoic acid of Syrian hamster embryo fibroblasts expressing v-src or v-Ha-ras oncogenes. Mol Cell Biol 6:3341–3348

    Google Scholar 

  • Land H, Parada LF, Weinburg RA (1983) Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature 304:596–602

    Google Scholar 

  • Lopez CA, Hsiao WL, Weinstein IB (1989) Effects of various chemical agents on the transformation of rat fibroblasts by an activated c-Ha-ras oncogene. Mol Carcinogen 2:81–87

    Google Scholar 

  • Lotan R (1980) Effects of vitamin A and its analogs (retinoids) on normal and neoplastic cells. Biochim Biophys Acta 605:33–91

    Google Scholar 

  • Lotan R (1986) Mechanisms of action of retinoids. Cancer Bull 38:113–116

    Google Scholar 

  • MacPherson I, Montagnier L (1964) Agar suspension culture for the selective assay of cells transformed by polyoma virus. Virology 23:291–294

    Google Scholar 

  • Maniatis T, Fritsch EF, Sambrook J (1982) Molecular cloning. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY

    Google Scholar 

  • Meeks RG, Zaharevitz D, Chen RF (1981) Membrane effects of retinoids: possible correlation with toxcity. Arch Biochem Biophys 207:141–147

    Google Scholar 

  • Palmer HJ, Maher VM, McCormick JJ (1989) Effect of retinoids on growth factor-induced anchorage independent growth of human fibroblasts. In Vitro Cell Dev Biol 25:1009–1015

    Google Scholar 

  • Rimoldi D, Samid D, Flessate DM, Friedman RM (1988) Transcriptional inhibition of Ha-ras in interferon-induced revertants ofras-transformed mouse cells. Cancer Res 48:5157–5162

    Google Scholar 

  • Roberts AB, Roche NS, Sporn MB (1985) Selective inhibition of the anchorage-independent growth ofmyc-transfected fibroblasts by retinoic acid. Nature 315:237–239

    Google Scholar 

  • Rutz HP, Little JB (1989) Retinoic acid inhibits the fixation of initial transformational damage in X-irradiated Balb/3T3 mouse fibroblasts in vitro. Carcinogenesis 10:2183–2186

    Google Scholar 

  • Shih C, Weinberg RA (1982) Isolation of a transforming sequence from a human bladder carcinoma cell line. Cell 29:161–169

    Google Scholar 

  • Southern PJ, Berg P (1982) Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. J Mol Appl Genet 1:327–341

    Google Scholar 

  • Stoner CM, Gudas LJ (1989) Mouse cellular retinoic acid binding protein: cloning, complementary DNA sequence, and messenger RNA expression during the retinoic acid-induced differentiation of F9 wild type and RA-3-10 mutant teratocarcinoma cells. Cancer Res 49:1497–1504

    Google Scholar 

  • Strain AJ (1987) The uptake and fate of DNA transfected into mammalian cells in vitro. Dev Biol Stand 68:27–32

    Google Scholar 

  • Thiele CJ, Deutsch LA, Israel MA (1988) The expression of multiple proto-oncogenes is differentially regulated during retinoic acid induced maturation of human neuroblastoma cell lines. Oncogene 3:281–288

    Google Scholar 

  • Tsang SS, Li G, Stich HF (1988) Effect of retinoic acid on bovine papillomavirus (BPV) DNA-induced transformation and number of BPV DNA copies. Int J Cancer 42:94–98

    Google Scholar 

  • Wigler M, Pellicer A, Silverstein S, Axel R, Urlaub G, Chasin L (1979) DNA-mediated transfer of the adenine phosphoribosyl-transferase locus into mammalian cells. Proc Natl Acad Sci 76:1373–1376

    Google Scholar 

  • Williams JG, Mason PJ (1985) Hybridization in the analysis of RNA. In: James BD, Higginds SJ (eds) Nucleic acid hybridization, a practical approach. IRL, Oxford, pp 139–148

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This investigation was supported by grants CA 52925, CA 13343 and ES 00260

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cox, L.R., Motz, J., Troll, W. et al. Effects of retinoic acid on NIH3T3 cell transformation by the H-ras oncogene. J Cancer Res Clin Oncol 117, 102–108 (1991). https://doi.org/10.1007/BF01613132

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01613132

Key words

Navigation