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.