PMID- 12060499
OWN - NLM
STAT- MEDLINE
DCOM- 20021204
LR  - 20111117
IS  - 1079-9907 (Print)
IS  - 1079-9907 (Linking)
VI  - 22
IP  - 5
DP  - 2002 May
TI  - Resistance to interferons in melanoma cells does not correlate with the 
      expression or activation of signal transducer and activator of transcription 1 
      (Stat1).
PG  - 603-13
AB  - Defects in expression or activation signal transducer and activator of 
      transcription-1 (Stat1) in response to interferon-alpha2 (IFN-alpha2) have been 
      implicated as a mechanism for IFN resistance in melanoma cells. To further 
      determine the significance of this observation, 17 melanoma cell lines sensitive 
      or resistant to the antiproliferative effects of IFN-alpha2 and IFN-beta, as well 
      as 30 melanoma patient samples, were analyzed for Stat1 levels by either Western 
      blot analysis or immunohistochemistry. Although the expression level varied 
      between samples, all the cell lines except one and all melanoma biopsy specimens 
      expressed Stat1. IFN-stimulated levels of Stat1 and Stat2, which constitute the 
      transcriptional activation complexes, such as, gamma activated factor (GAF) and 
      IFN-stimulated gene factor 3 (ISGF3), for IFN-stimulated gene (ISG) induction 
      were assessed in melanoma cell lines. Both IFN-alpha2 and INF-beta induced 
      equivalent amounts of Stat1 and Stat2 proteins in cell lines, although compared 
      with IFN-alpha2, IFN-beta had greater antiproliferative effects. No significant 
      differences were observed in tyrosine or serine phosphorylation of Stat1 or the 
      formation of GAF or ISGF3 complexes following IFN-alpha2 or IFN-beta treatment of 
      IFN-resistant or IFN-sensitive cell lines. Comparable induction of two ISGs, 
      ISG54 and IFN regulatory factor-1 (IRF-1), was observed in both sensitive WM9 and 
      resistant A375 cells. Therefore, we report that defects in expression or 
      activation of Stat1 or Stat2 were infrequent in melanoma cell lines and tumor 
      samples and did not correlate with IFN resistance. Cellular resistance to IFNs 
      likely results from defective quantitative or qualitative expression of specific 
      ISGs.
FAU - Chawla-Sarkar, Mamta
AU  - Chawla-Sarkar M
AD  - Center for Drug Discovery and Development, Taussig Cancer Center, Cleveland, OH 
      44195, USA.
FAU - Leaman, Douglas W
AU  - Leaman DW
FAU - Jacobs, Barbara S
AU  - Jacobs BS
FAU - Tuthill, Ralph J
AU  - Tuthill RJ
FAU - Chatterjee-Kishore, Moitreyee
AU  - Chatterjee-Kishore M
FAU - Stark, George R
AU  - Stark GR
FAU - Borden, Ernest C
AU  - Borden EC
LA  - eng
GR  - CA90914/CA/NCI NIH HHS/United States
GR  - P01 CA62220/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Interferon Cytokine Res
JT  - Journal of interferon & cytokine research : the official journal of the 
      International Society for Interferon and Cytokine Research
JID - 9507088
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (IRF9 protein, human)
RN  - 0 (Interferon Type I)
RN  - 0 (Interferon-Stimulated Gene Factor 3)
RN  - 0 (Interferon-Stimulated Gene Factor 3, gamma Subunit)
RN  - 0 (Recombinant Proteins)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (STAT1 protein, human)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Cell Division/drug effects
MH  - DNA-Binding Proteins/chemistry/*genetics/*metabolism
MH  - Dimerization
MH  - Drug Resistance, Neoplasm
MH  - Gene Expression/drug effects
MH  - Humans
MH  - Interferon Type I/*pharmacology
MH  - Interferon-Stimulated Gene Factor 3
MH  - Interferon-Stimulated Gene Factor 3, gamma Subunit
MH  - Melanoma/*drug therapy/genetics/*metabolism/pathology
MH  - Recombinant Proteins
MH  - STAT1 Transcription Factor
MH  - Trans-Activators/chemistry/*genetics/*metabolism
MH  - Transcription Factors/genetics/metabolism
MH  - Tumor Cells, Cultured
EDAT- 2002/06/13 10:00
MHDA- 2002/12/05 04:00
CRDT- 2002/06/13 10:00
PHST- 2002/06/13 10:00 [pubmed]
PHST- 2002/12/05 04:00 [medline]
PHST- 2002/06/13 10:00 [entrez]
AID - 10.1089/10799900252982089 [doi]
PST - ppublish
SO  - J Interferon Cytokine Res. 2002 May;22(5):603-13. doi: 10.1089/10799900252982089.