Identification of locus-specific DNA-binding factors for the regulation of HLA class-I genes in human colorectal cancer.
The expression of HLA class-I mRNA in human colorectal cancer cell lines was studied. Locus-specific down-regulation of HLA class-I mRNA could be demonstrated in some of the human colorectal lines. This transcriptional suppression of HLA mRNA, however, was not a result of genetic alterations in the HLA structural genes. The transcription of the HLA class-I genes in the HLA-deficient cell lines could be induced by the addition of human recombinant gamma-IFN. In this report, we have employed these human colorectal cell lines to study locus-specific transcriptional regulation of HLA class-I gene expression. Our results demonstrate that the locus-specific suppression of HLA gene expression in human colorectal cell lines is mediated by the loss of certain DNA-binding transcription factors which act in a locus-specific manner. Our conclusion is further supported by experiments which showed that exogenously introduced HLA-CAT DNA constructs were also regulated in a locus-specific fashion when assayed by in vitro functional assays using these human colorectal cell lines.
Soong
T W
TW
Institute of Molecular and Cell Biology, National University of Singapore, Kent Ridge.
Hui
K M
KM
D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D005805:Genes, MHC Class I; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012004:Rectal Neoplasms / Q000235:genetics / Q000276:immunology*; D014158:Transcription, Genetic; D014162:Transfection
D004268:DNA-Binding Proteins; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D015500:Chloramphenicol O-Acetyltransferase