Malignant melanoma associates with deficient IFN-induced STAT 1 phosphorylation

  • Authors:
    • Jan Kovarik
    • V. Boudny
    • I. Kocak
    • L. Lauerova
    • V. Fait
    • M. Vagundova
  • View Affiliations

  • Published online on: September 1, 2003     https://doi.org/10.3892/ijmm.12.3.335
  • Pages: 335-340
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Abstract

STAT 1, a member of signal transducers and transcription activators of STAT family proteins, has been implicated as important mediator of IFN signaling. Functional activation of STAT 1 requires tyrosine and serine phosphorylation. Defects in its expression or activation in response to IFNs were observed in numerous pathological conditions including cancer. To further explore cancer-associated impaired STAT 1 response to IFNs, the inducibility of serine (S 727) and tyrosine (Y 701) phosphorylation by IFN-α/-γ was assessed in 21 melanoma cell lines and in 35 primary cultures derived from melanoma patients. STAT 1 levels and inducibility of its activated phospho-forms were detected by Western analysis using specific polyclonal and monoclonal antibodies. All cell lines as well as patient melanoma samples expressed STAT 1 with variable signal intensity. Significant impaired IFN-induced STAT 1 S 727 phosphorylation was observed in both model systems with average of 77% of non-responders recorded in patient melanoma cells and 76% in melanoma cell lines. Failure of PY 701 induction occurred in patient samples (63% after IFN-α and 34% after IFN-γ induction) and to a lesser degree in cell lines (i.e. response absence to IFN-α in 5 and to IFN-γ in 2 melanoma lines). Our study demonstrates STAT 1 functional abnormalities in melanoma cells. On the basis of detailed analyses of patient melanoma cells with respect to the inducibility of STAT 1 phosphorylation by IFNs, four categories of patients could be distinguished: a) activation on both S 727 and Y 701, b) not inducible response, c) activation on Y 701 but not on S 727, d) heterogeneous response. Clinical study is now in progress to establish the significance of in vitro STAT 1 activation for predicting the response to IFN-based therapy and to explore biological consequences in cases responding in vitro to IFN-induced STAT 1 activation on only one of the critical amino acid residues.

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September 2003
Volume 12 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Kovarik J, Boudny V, Kocak I, Lauerova L, Fait V and Vagundova M: Malignant melanoma associates with deficient IFN-induced STAT 1 phosphorylation. Int J Mol Med 12: 335-340, 2003
APA
Kovarik, J., Boudny, V., Kocak, I., Lauerova, L., Fait, V., & Vagundova, M. (2003). Malignant melanoma associates with deficient IFN-induced STAT 1 phosphorylation. International Journal of Molecular Medicine, 12, 335-340. https://doi.org/10.3892/ijmm.12.3.335
MLA
Kovarik, J., Boudny, V., Kocak, I., Lauerova, L., Fait, V., Vagundova, M."Malignant melanoma associates with deficient IFN-induced STAT 1 phosphorylation". International Journal of Molecular Medicine 12.3 (2003): 335-340.
Chicago
Kovarik, J., Boudny, V., Kocak, I., Lauerova, L., Fait, V., Vagundova, M."Malignant melanoma associates with deficient IFN-induced STAT 1 phosphorylation". International Journal of Molecular Medicine 12, no. 3 (2003): 335-340. https://doi.org/10.3892/ijmm.12.3.335