Skip to main content
SpringerLink
Log in

Interferon Regulatory Factor-1 and -2 Expression in Human Melanoma Specimens

  • Original Article
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background: Interferon regulatory factor (IRF)-1 and IRF-2 are nuclear transcription factors that respond to interferon-γ. IRF-1 acts as the effector arm of the interferon-γresponse in tumor cells, whereas IRF-2 binds to the same DNA consensus sequence and opposes IRF-1 activity. This effect is intact in human and murine tumor models, including melanomas; previous work in our laboratory demonstrated the tumor-suppressing activity of IRF-1 expression in in vivo models and the opposing effect of IRF-2. The expression of IRF-1 and -2 in human solid tumors had not been previously investigated.

Methods: Formalin-fixed, paraffin-embedded, archival tissue specimens from 38 human melanomas were obtained and stained with polyclonal anti-IRF-1 and anti-IRF-2 antibodies, using an avidin-biotin-peroxidase complex technique with epitope retrieval.

Results: Twenty-nine specimens showed granular cytoplasmic staining with the anti-IRF-1 or anti-IRF-2 antibodies. IRF-1 staining was correlated with less advanced disease. Superficial spreading and in situ lesions exhibited more frequent IRF-1 staining, compared with nodular or metastatic disease. Only more advanced lesions showed neither IRF-1 nor IRF-2 staining.

Conclusions: Immunohistochemical staining of archival tissue identified IRF-1 and -2 in human melanomas; this had not been previously demonstrated. IRF-1 staining was correlated with the morphologic characteristics of less advanced disease. Tumor-suppressing effects of IRF-1 may account for the less aggressive biologic features of IRF-1-expressing melanomas, as we would predict from the experimental data.

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

Access this article

Log in via an institution

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. Dighe AS, Richards E, Old LJ, Schreiber RD. Enhanced in vivo growth and resistance to rejection of tumor cells expressing dominant negative IFN-gamma receptors. Immunity 1994;1:447–456.

    Article  CAS  PubMed  Google Scholar 

  2. Doherty GM, Tsung K, McCluskey B, Norton JA. Endogenous interferon gamma acts directly on tumor cells in vivo to suppress growth. J Surg Res 1996;64:68–74.

    Google Scholar 

  3. Kirkwood JM, Strawderman MH, Ernstoff MS, Smith TJ, Borden EC, Blum RH. Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. J Clin Oncol 1996;14:7–17.

    Google Scholar 

  4. Geller DA, Nguyen D, Shapiro RA, et al. Cytokine induction of interferon regulatory factor-1 in hepatocytes. Surgery 1993;114:235–242.

    Google Scholar 

  5. Pine R. Constitutive expression of an ISGF2/IRF1 transgene leads to interferon-independent activation of interferon-inducible genes and resistance to virus infection. J Virol 1992;66:4470–4478.

    Google Scholar 

  6. Coccia EM, Marziali G, Stellacci E, et al. Cells resistant to interferon-beta respond to interferon-gamma via the STAT1-IRF-1 pathway. Virology 1995;211:11–122.

    Google Scholar 

  7. Kamijo R, Harada H, Matsuyama T, et al. Requirement for transcription factor IRF-1 in NO synthase induction in macrophages. Science 1994;263:1612–1615.

    Google Scholar 

  8. Martin E, Nathan C, Xie Q-W. Role of interferon regulatory factor 1 in induction of nitric oxide synthase. J Exp Med 1994;180:977–984

    Google Scholar 

  9. Briken V, Ruffner H, Schultz U, et al. Interferon regulatory factor 1 is required for mouse gbp gene activation by gamma interferon. Mol Cell Biol 1995;15:975–982.

    Google Scholar 

  10. Chang C-H, Hammer J, Loh JE, Fodor WL, Flavell RA. The activation of major histocompatibility complex class I genes by interferon regulatory factor-1 (IRF-1). Immunogenetics 1992;35:378–384.

    Google Scholar 

  11. Lim SP, Hui KM. Characterization of a novel IRF-1 deficient mutant cell line. Immunogenetics 1994;39:168–177.

    Google Scholar 

  12. Reis LFL, Harada H, Wolchok JD, Taniguchi T, Vilcek J. Critical role of a common transcription factor, IRF-1, in the regulation of IFN-beta and IFN-inducible genes. EMBO J 1992;11:185–193.

    Google Scholar 

  13. Hobart M, Ramassar V, Goes N, Urmson J, Halloran PF. IFN regulatory factor-1 plays a central role in the regulation of the expression of class I and II MHC genes in vivo. J Immunol 1997;158:4260–4269.

    Google Scholar 

  14. Hobart M, Ramassar V, Goes N, Urmson J, Halloran PF. The induction of class I and II major histocompatibility complex by allogeneic stimulation is dependent on the transcription factor interferon regulatory factor 1 (IRF-1). Transplantation 1996;62:1895–1901.

    Google Scholar 

  15. Yim JH, Wu SJ, Casey MJ, Norton JA, Doherty GM. Interferon regulatory factor-1 gene transfer into an aggressive, nonimmunogenic sarcoma suppresses the malignant phenotype and enhances immunogenicity in syngeneic mice. J Immunol 1997;158:1284–1292.

    Google Scholar 

  16. Harada H, Willison K, Sakakibara J, Miyamoto M, Fujita T, Taniguchi T. Absence of the type 1 IFN system in EC cells: transcriptional activator (IRF-1) and repressor (IRF-2) genes are developmentally regulated. Cell 1990;63:303–312.

    Google Scholar 

  17. Fujita T, Kimura Y, Miyamoto M, Barsoumian EL, Taniguchi T. Induction of endogenous IFN-alpha and IFN-beta genes by a regulatory transcription factor, IRF-1. Nature 1989;337:270–272.

    Article  CAS  PubMed  Google Scholar 

  18. Harada H, Kitagawa M, Tanaka N, et al. Anti-oncogenic and oncogenic potentials of interferon regulatory factors-1 and -2. Science 1993;259:971–974.

    Google Scholar 

  19. Doherty GM, McCluskey B, Tsung K, Norton JA. Correlation of interferon regulatory factors 1 and 2 (IRF-1 and -2): expression and murine tumor growth in the presence of interferon-gamma. Surg Forum 1995;46:544–546.

    Google Scholar 

  20. Yim JH, Wu SJ, Lowney JK, Vander Velde TL, Doherty GM. Enhancing in vivo tumorigenicity of B16 melanoma by overexpressing interferon regulatory factor-2: resistance to endogenous interferon-γ. J Interferon Cytokine Res (in press).

  21. Willman CL, Sever CE, Pallavicini MG, et al. Deletion of IRF-1, mapping to chromosome 5q31.1, in human leukemia and preleukemic myelodysplasia. Science 1993;259:968–70.

    Google Scholar 

  22. Tamura G, Ogasawara S, Nishizuka S, et al. Two distinct regions of deletion on the long arm of chromosome 5 in differentiated adenocarcinomas of the stomach. Cancer Res 1996;56:612–5.

    Google Scholar 

  23. Ogasawara S, Tamura G, Maesawa C, et al. Common deleted region on the long arm of chromosome 5 in esophageal carcinoma. Gastroenterology 1996;110:52–7.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, Washington University, St. Louis, Missouri

    Jennifer K. Lowney MD & Gerard M. Doherty MD

  2. Department of Pathology, Washington University, St. Louis, Missouri

    Leslie D. Boucher MD & Paul E. Swanson MD

  3. Department of Surgery, Washington University, 660 South Euclid Avenue, St. Louis, MO, 63110

    Gerard M. Doherty MD

Authors
  1. Jennifer K. Lowney MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Leslie D. Boucher MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paul E. Swanson MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gerard M. Doherty MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gerard M. Doherty MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lowney, J.K., Boucher, L.D., Swanson, P.E. et al. Interferon Regulatory Factor-1 and -2 Expression in Human Melanoma Specimens. Ann Surg Oncol 6, 604–608 (1999). https://doi.org/10.1007/s10434-999-0604-4

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10434-999-0604-4

Key Words

Search

Navigation