Skip to main content
Log in

Interferon-alpha and gamma mediated gene responses in a human breast carcinoma cell line

  • Report
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Interferons (IFNs) have been known to possess an antiproliferative effect on tumor cells besides their well characterized antiviral effect in cell cultures. The mechanism of action of the different IFNs is not fully understood, but in recent years a number of IFN-inducible genes, the presumed mediators of IFN action, have been identified. In the present study we examined the antiproliferative effect of IFN-alpha and IFN-gamma on human breast cancer cells (MCF-7) using (i) the MTT dye formation assay and (ii) anchorage-independent (AI) growth in soft agar. Both IFN-alpha and IFN-gamma were found to have an antiproliferative effect on the growth of MCF-7 cells. In addition, the kinetics of induction of a number of IFN-inducible genes was also examined. The expression of these genes was measured by mRNA analyses using specific [alpha-32P]-labeled cDNAs as probes. The induction of these genes by IFN-alpha and IFN-gamma is a primary effect of IFN, asde novo protein synthesis is not required for their induction. Our results on the kinetics of induction of these genes by IFN-alpha and IFN-gamma suggests a complex mechanism of ligand-dependent gene activation in this cell line with some similar and dissimilar pathways.

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

References

  1. Pestka S, Langer JA, Zoon KA, Samuel CE: Interferons and their action. Ann Rev Biochem 56: 727–767, 1982

    Article  Google Scholar 

  2. Lengyel P: Biochemistry of interferons and their actions. Ann Rev Biochem 51: 251–282, 1982

    Article  PubMed  Google Scholar 

  3. Sen GC: Biochemical pathways in interferon action. Pharmacol Therap 24: 235–257, 1984

    Article  Google Scholar 

  4. Friedman RL, Manly SP, McMahon M, Kerr IM, Stark GR: Transcriptional and post transcriptional regulation of interferon induced gene expression in human cells. Cell 38: 745–755, 1984

    Article  PubMed  Google Scholar 

  5. Kusari J, Sen GC: Transcriptional analysis of interferon inducible mRNAs. Mol Cell Biol 7: 528–531, 1987

    PubMed  Google Scholar 

  6. Merlin G, Chebath J, Benech P, Metz R, Revel H: Molecular cloning and sequence of partial cDNA for interferon induced (2′–5′) oligo (A) synthetase mRNA from human cells. Proc Natl Acad Sci USA 80: 4904–4908, 1983

    PubMed  Google Scholar 

  7. Chebath J, Benech M, Revel M, Vigneron M: Constitutive expression of (2′–5′) oligo A synthetase confers resistence to picornavirus infection. Nature (London) 330: 587–588, 1987

    Article  PubMed  Google Scholar 

  8. Tiwari RK, Kusari J, Sen GC: Functional equivalents of interferon mediated signals needed for induction of an mRNA can also be generated by double-stranded RNA and growth factors. EMBO J 6: 3373–3378, 1987

    PubMed  Google Scholar 

  9. Wathelet MG, Moutschen S, Defilippi P, Cravador A, Collet M, Huez G, Content J: Molecular cloning: full length sequence and preliminary characterization of a 56 kDa protein induced by human interferons. Eur J Biochem 155: 1–7, 1986

    Article  PubMed  Google Scholar 

  10. Edmondson JM, Armstrong LS, Martinez AO: A rapid and simple MTT based spectrophotometric assay for determining drug sensitivity in monolayer cultures. J Tissue Culture Methods 11: 15–17, 1988

    Article  Google Scholar 

  11. White BA, Bancroft FC: Cytoplasmic dot hybridization. Simple analysis of relative mRNA levels in multiple small cell or tissue samples. J Biol Chem 257: 8569–8572, 1982

    PubMed  Google Scholar 

  12. Tiwari RK, Kusari J, Kumar R, Sen GC: Gene induction by interferons and double stranded RNA: selective inhibition by 2-aminopurine. Mol Cell Biol 8: 4289–4294, 1988

    PubMed  Google Scholar 

  13. Cleveland DW, Lopata MA, MacDonald RJ, Cowan NJ, Rutter WJ, Kirschner MW: Number and evolutionary conservation of α and β tubulin and cytoplasmic β and gamma actin genes using specific cloned cDNA probes. Cell 20: 95–105, 1980

    Article  PubMed  Google Scholar 

  14. Greiner JW, Hand PH, Noguchi P, Fisher PB, Pestka S, Schlom J: Enhanced expression of surface tumor associated antigens on human breast and colon tumor cells after recombinant human leukocyte α-interferon treatment. Cancer Res 44: 3208–3214, 1984

    PubMed  Google Scholar 

  15. Goldstein D, Bushmeyer SM, Witt PL, Jordan VC, Borden EC: Effects of type I and II interferons on breast cancer cells: interaction with estrogen receptor and with tamoxifen. Cancer Res 49: 2698–2702, 1989

    PubMed  Google Scholar 

  16. Sica G, Natoli V, Stella C, Bianco S: Effect of natural beta-interferon on cell proliferation and steroid receptor level in human breast cancer cells. Cancer 60: 2419–2423, 1987

    PubMed  Google Scholar 

  17. Caplen HC, Gupta SL: Differential regulation of a cellular gene by human interferon-gamma and interferon-alpha. J Biol Chem 263: 332–339, 1988

    PubMed  Google Scholar 

  18. Levy DE, Kessler DS, Pine R, Reich N, Darnell JE: Interferon induced nuclear factors that bind a shared promoter element correlate with positive and negative transcriptional control. Genes Devel 2: 383–393, 1988

    PubMed  Google Scholar 

  19. Larner AC, Jonak G, Cheng YSE, Kovant B, Knight F, Darnell JE: Transcriptional induction of two genes in human cells by beta-interferon. Proc Natl Acad Sci USA 81: 6733–6737, 1984

    PubMed  Google Scholar 

  20. Decker T, Lew DJ, Cheng YSE, Levy DE, Darnell JE: Interactions of alpha and gamma interferon in the transcriptional regulation of the gene encoding a guanylate binding protein. EMBO J 8: 2009–2014, 1989

    PubMed  Google Scholar 

  21. Luster AD, Unkeless JC, Ravetch JV: Alpha-interferon transcriptionally regulates an early response gene containing homology to platelet proteins. Nature (London) 315: 672–676, 1985

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tiwari, R.K., Wong, G.Y., Mukhopadhyay, B. et al. Interferon-alpha and gamma mediated gene responses in a human breast carcinoma cell line. Breast Cancer Res Tr 18, 33–41 (1991). https://doi.org/10.1007/BF01975441

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01975441

Key words

Navigation