Cell-type specificity of interferon-gamma-mediated HLA class I gene transcription in human hematopoietic tumor cells.
Major histocompatibility complex class I gene expression plays a central role in cellular immunity and tumor surveillance. A substantial proportion of spontaneous tumors are class I-deficient and numerous experiments have suggested that alterations in class I expression may alter oncogenicity and, as a result, have potential therapeutic impact. Interferons (IFNs) are able to upregulate class I expression by mechanisms that remain to be elucidated, but which appear to be IFN- and cell-type specific. We have characterized in detail the in vivo class I transcriptional response to IFN-gamma in two human hematopoietic tumor cell lines, the class I-deficient K562 cell line and the class I-positive Ramos cell line. In each, IFN-gamma induces a rapid increase in class I transcription, which is sustained in Ramos cells, but transient in K562 cells. In each, stimulation by IFN-gamma is dependent on ongoing protein synthesis, suggesting the requirement for production of a "primary response" protein. These data suggest that more than one type of IFN-gamma-induced signal is operative in the transcriptional response to IFN-gamma. Cycloheximide alone is also capable of inducing a rapid increase in class I transcription in both cell types, suggesting that constitutive attenuation of class I transcription may be a common phenomenon, and that IFN-gamma may act, in part, by interfering with such attenuation.
Radford
J E
JE
Department of Internal Medicine, University of Iowa, Iowa City.
Chen
E
E
Hromas
R
R
Ginder
G D
GD
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D006410:Hematopoiesis; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D007700:Kinetics; D011994:Recombinant Proteins; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D011994:Recombinant Proteins; D007371:Interferon-gamma; D003513:Cycloheximide