Fol. Biol. 2003, 49, 142-146
Interferon Inducibility of STAT 1 Activation and Its Prognostic Significance in Melanoma Patients
STAT 1, a member of latent cytoplasmic proteins, plays a pivotal role in mediating biological effects of interferons. Its transducing, DNA binding and transcriptional activity require phosphorylation at both Tyr 701 (Y 701) and Ser 727 (S 727) residues. Deficient phosphorylation or constitutive activation of the STAT 1 protein were observed in some human malignancies. Using immunoprecipitation and Western blots performed with lysates made of melanoma cells derived from patients with clinical stage II/III and employing specific anti-STAT 1 PS 727/PY 701 immunoprobes, we show that STAT 1 activation response induced by IFN-α/-γ is significantly impaired. On average, three quarters of patients were lacking phosphorylation at S 727. STAT 1 PY 701 was not inducible by IFN-α in 63% and by IFN-γ in 34% of samples. However, these STAT 1 activation defects showed no correlation with the disease outcome and immunotherapy response as indicated by progression-free survival profiles in patients treated with IFN-α2b.
Keywords
STAT 1, malignant melanoma, signal transduction, interferons.
Funding
The study was supported in part by Grant NC/7139-3 from the Internal Grant Agency of the Czech Ministry of Health, Grant 301/00/0564 from the Grant Agency of the Czech Republic and by Institutional Project No. MZ 00020980501.
References
Copyright
This is an open-access article distributed under the terms of the Creative Commons Attribution License.