Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
45
pubmed:dateCreated
1997-12-12
pubmed:abstractText
The mechanism of IFN resistance was examined in three long-term cell lines, SK-MEL-28, SK-MEL-3, and MM96, exhibiting significant variation in responsiveness to the antiproliferative and antiviral effects of type I IFNs. The JAK-STAT components involved in IFN signal transduction were analyzed in detail. After exposure to IFN, activation of the IFN type I receptor-linked tyrosine kinases, JAK-1 and TYK-2, was detected at similar levels in both IFN-sensitive and IFN-resistant cell types, indicating that IFN resistance did not result from a deficiency in signaling at the level of receptor-associated kinase activation. However, analysis of ISGF3 transcription factor components, STAT1, STAT2, and p48-ISGF3gamma, revealed that their expression and activation correlated with cellular IFN responsiveness. The analysis was extended to also include IFN-sensitive primary melanocytes, three additional IFN-resistant melanoma cell lines, and seven cell cultures recently established from melanoma patient biopsies. It was consistently observed that the most marked difference in ISGF3 was a lack of STAT1 in the resistant versus the sensitive cells. Transfection of the IFN-resistant MM96 cell line to express increased levels of STAT1 protein partially restored IFN responsiveness in an antiviral assay. We conclude that a defect in the level of STAT1 and possibly all three ISGF3 components in IFN-resistant human melanoma cells may be a general phenomenon responsible for reduced cellular responsiveness of melanomas to IFNs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, http://linkedlifedata.com/resource/pubmed/chemical/Cytokines, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/IRF9 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/ISG15 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Interferon-Stimulated Gene Factor 3, http://linkedlifedata.com/resource/pubmed/chemical/Interferon-Stimulated Gene Factor..., http://linkedlifedata.com/resource/pubmed/chemical/Interferon-alpha, http://linkedlifedata.com/resource/pubmed/chemical/Interferons, http://linkedlifedata.com/resource/pubmed/chemical/JAK1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 1, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Proteins, http://linkedlifedata.com/resource/pubmed/chemical/STAT1 Transcription Factor, http://linkedlifedata.com/resource/pubmed/chemical/STAT1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/STAT2 Transcription Factor, http://linkedlifedata.com/resource/pubmed/chemical/STAT2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/TYK2 Kinase, http://linkedlifedata.com/resource/pubmed/chemical/TYK2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine, http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitins
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
272
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
28779-85
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:9353349-Antineoplastic Agents, pubmed-meshheading:9353349-Cytokines, pubmed-meshheading:9353349-DNA-Binding Proteins, pubmed-meshheading:9353349-Drug Resistance, Neoplasm, pubmed-meshheading:9353349-Humans, pubmed-meshheading:9353349-Interferon-Stimulated Gene Factor 3, pubmed-meshheading:9353349-Interferon-Stimulated Gene Factor 3, gamma Subunit, pubmed-meshheading:9353349-Interferon-alpha, pubmed-meshheading:9353349-Interferons, pubmed-meshheading:9353349-Janus Kinase 1, pubmed-meshheading:9353349-Melanoma, pubmed-meshheading:9353349-Phosphorylation, pubmed-meshheading:9353349-Protein-Tyrosine Kinases, pubmed-meshheading:9353349-Proteins, pubmed-meshheading:9353349-STAT1 Transcription Factor, pubmed-meshheading:9353349-STAT2 Transcription Factor, pubmed-meshheading:9353349-Signal Transduction, pubmed-meshheading:9353349-TYK2 Kinase, pubmed-meshheading:9353349-Trans-Activators, pubmed-meshheading:9353349-Transcription Factors, pubmed-meshheading:9353349-Tumor Cells, Cultured, pubmed-meshheading:9353349-Tyrosine, pubmed-meshheading:9353349-Ubiquitins
pubmed:year
1997
pubmed:articleTitle
Interferon-resistant human melanoma cells are deficient in ISGF3 components, STAT1, STAT2, and p48-ISGF3gamma.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, Monash University, Wellington Road, Clayton, Victoria 3168, Australia.
pubmed:publicationType
Journal Article