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Development of IFN-γ resistance is associated with attenuation of SOCS genes induction and constitutive expression of SOCS 3 in melanoma cells
- Source :
- British Journal of Cancer
- Publication Year :
- 2007
- Publisher :
- Springer Science and Business Media LLC, 2007.
-
Abstract
- The resistance to interferons (IFNs) limits their anticancer therapeutic efficacy. Here we studied the evolution of an IFN-resistant state in vitro using melanoma cell lines. We found that the cells became less sensitive to antiproliferative effect of IFN-gamma after prolonged cultivation enabling us to isolate sensitive and resistant subclones of the parental line. We investigated transcription of signal transducer and activator of transcription (STAT) 1-6 and suppressor of cytokine signalling (SOCS) 1-3 genes, and phosphorylation of STAT 1 protein. The resistant subline (termed WM 1158R) differed from the sensitive subline (WM 1158S) by a constitutive expression of SOCS 3, lack or weak SOCS 1-3 activation following IFN-gamma, and short duration of cytokine activatory signal. Similar correlations were observed in additional melanoma lines differing in IFN sensitivities. At the protein level, IFN-gamma induced strong and prolonged STAT 1 activation at serine 727 (S727) in WM 1158R while in WM 1158S cells phosphorylation of this amino acid was much less pronounced. On the other hand, phosphorylation of tyrosine 701 (Y701) was stimulated regardless of the sensitivity phenotype. In conclusion, constitutive expression of SOCS 3 is correlated with attenuation of its induction following IFN treatment. These results suggest that progression of melanoma cells from IFN sensitivity to IFN insensitivity associates with changes in SOCS expression.
- Subjects :
- Cancer Research
Skin Neoplasms
interferon resistance
medicine.medical_treatment
malignant melanoma
Gene Expression
Suppressor of Cytokine Signaling Proteins
Biology
Suppressor of cytokine signalling
stat
Interferon-gamma
03 medical and health sciences
0302 clinical medicine
Cell Line, Tumor
Gene expression
medicine
Humans
Phosphorylation
Molecular Diagnostics
Melanoma
STAT phosphorylation
Cell Proliferation
030304 developmental biology
Regulation of gene expression
0303 health sciences
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
SOCS proteins
STAT1 Transcription Factor
Cytokine
Oncology
Drug Resistance, Neoplasm
Suppressor of Cytokine Signaling 3 Protein
030220 oncology & carcinogenesis
STAT protein
Cancer research
Signal transduction
Subjects
Details
- ISSN :
- 15321827 and 00070920
- Volume :
- 97
- Database :
- OpenAIRE
- Journal :
- British Journal of Cancer
- Accession number :
- edsair.doi.dedup.....a727ef4accc71354e212585dbd0ed8f0