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Role of the interferon-stimulated response element in HLA-B downregulation in human melanoma cell lines.
- Source :
-
Immunogenetics [Immunogenetics] 1999 Apr; Vol. 49 (4), pp. 287-94. - Publication Year :
- 1999
-
Abstract
- Tumor cells are thought to escape immune surveillance from T cells by suppressing expression of major histocompatibility complex (MHC) class I molecules at their cell surface. Human MHC class I molecules are encoded by three different loci (HLA-A, -B, and -C). In primary human melanomas as well as melanoma cell lines, HLA class I expression is frequently downregulated in a B locus-specific manner. To study the involvement of promoter elements in HLA-B locus-specific downregulation, a series of reporter constructs containing 5'-flanking sequences of the HLA-A2 and -B7 genes were transfected into melanoma cell lines expressing high and low levels of HLA-B antigens. It is shown that enhancer A, which is generally believed to be a potent enhancer in HLA class I gene transcription, only weakly activates transcription in melanoma cell lines. In contrast, the interferon-stimulated response element (ISRE), known to induce MHC class I expression in response to IFNs, as well as a region comprising site alpha/enhancer B significantly stimulate constitutive transcription of HLA class I genes. Although none of the promoter elements tested could be demonstrated to mediate HLA-B locus-specific downregulation, high and low HLA-B melanoma cell lines do differ in ISRE activity as well as in ISRE-binding nuclear factors. The finding that high and low HLA-B melanoma cell lines contain different transcription factors binding to elements not actively involved in the process of HLA-B locus abrogation suggests that these cell lines originate from distinct types of melanocyte precursor cells expressing a different set of transcription factors.
- Subjects :
- Binding Sites
DNA-Binding Proteins biosynthesis
Down-Regulation
Electrophoresis, Polyacrylamide Gel
Humans
Interferon Regulatory Factor-2
Melanoma immunology
Promoter Regions, Genetic
Transcription, Genetic
Tumor Cells, Cultured
Gene Expression Regulation, Neoplastic
HLA-A2 Antigen genetics
HLA-B7 Antigen genetics
Interferons
Melanoma genetics
Repressor Proteins
Response Elements
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 0093-7711
- Volume :
- 49
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Immunogenetics
- Publication Type :
- Academic Journal
- Accession number :
- 10079292
- Full Text :
- https://doi.org/10.1007/s002510050495