Neoplasma Vol.52, p.330-337, 2005
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| Title: Lack of STAT 1 phosphorylation at TYR 701 by IFN correlates with
disease outcome in melanoma patients
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| Author: V., BOUDNY
; L., DUSEK
; L., ADAMKOVA
; J., CHUMCHALOVA
; I., KOCAK
; V., FAIT
; L., LAUEROVA
; E., KREJCI
; J., KOVARIK
; |
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Abstract: STAT 1, a member of signal transducer and transcription activator
family has been implicated as key downstream mediator
of interferon (IFN) signaling. Its functional activation requires
phosphorylation at Tyr 701 and Ser 727 residues. Various
STAT abnormalities have been found in cancer cells but their
relation to oncogenesis, tumor behavior and disease outcome
remains mostly unknown. We have examined the inducibility of STAT
1 phosphorylation by IFN alpfa/gamma in primary cultures
established from melanoma lymph node metastases at first
progression and correlated our results with disease outcome and
overall survival. Forty-four patients at clinical stage I–III at
initial diagnosis entered the study. STAT 1 inducibility of
phosphorylation by IFNs was assessed in melanoma cell lysates by
means of standard immunoprecipitation and Western
blotting using polyclonal and monoclonal antibodies. Lack of STAT
1 phosphorylation at Ser 727 after either IFN was recorded
in 75% of patients, however, no correlations with disease
evolution could be proved. In contrast, STAT 1
phosphorylation response at Tyr 701 after IFNalpha occurred in 13
(29.5%) and after IFNgamma in 32 (73%) patients. Inducibility of
STAT 1 activation at Tyr 701 but not at Ser 727 driven by IFNgamma but
not by IFNalpha significantly and favorably influenced disease-
free interval and overall survival. In conclusion, these results
show that the absence of IFNgamma inducibility of STAT 1
phosphorylation at Tyr 701 positively correlates with disease
outcome in malignant melanoma patients and may represent
new independent prognostic marker.
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| Keywords: STAT 1 activation, interferons, malignant melanoma, disease
prognosis
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| Year: 2005, Volume: 52, Issue: |
Page From: 330, Page To: 337 |
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