Induction of ICAM-1 and HLA-DR expression by IFN-gamma in malignant melanoma cell lines.
Two human malignant melanoma cell lines, Malme-3M and SK-Mel-28, were analyzed for their ability to induce the expression of intercellular adhesion molecule 1 (ICAM-1) and human leukocyte antigen (HLA)-DR molecules on their cell surfaces as well as at the transcriptional level before and after treatment with interferon (IFN)-gamma. Both cell lines demonstrated a high percentage (> 99%) of ICAM-1 expression regardless of IFN-gamma treatment. Before IFN-gamma treatment, Malme-3M cells barely expressed HLA-DR molecules (< 2%) and SK-Mel-28 cells demonstrated a relatively high percentage (> 50%) of HLA-DR expression. Both cell lines displayed elevated levels of HLA-DR expression in a time dependent manner after IFN-gamma treatment. However, these two cell lines have been shown to respond differentially to IFN-gamma. The molecular mechanism underlying such a differential behavior was investigated, and HLA-DR gene regulation was studied at the transcriptional level. Treatment with IFN-gamma led to the steady-state mRNA augmentation of the HLR-DR gene. The HLA-DRA mRNA augmentation was similar in both cell lines, whereas in Malme-3M, IFN-gamma did not augment the rate of transcription of the HLA-DRB gene as much as in SK-Mel-28. Data from this study established the fact that the melanoma cell lines displayed a differential susceptibility to IFN-gamma on the modulation of HLA-DR molecules, and this modulation was transcriptionally regulated.
Kim
J D
JD
Department of Microbiology, Yonsei University College of Medicine, Seoul, Korea.
Lee
J L
JL
Park
J H
JH
Lee
J M
JM
Kim
Y H
YH
Kim
S J
SJ
D005802:Genes, MHC Class II; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D006684:HLA-DR Antigens; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma