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Identification of locus‐specific DNA‐binding factors for the regulation of HLA class‐I genes in human colorectal cancer
Author(s) -
Soong Tuck W.,
Hui Kam M.
Publication year - 1991
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910470724
Subject(s) - human leukocyte antigen , locus (genetics) , biology , gene , genetics , transcription (linguistics) , dna , gene expression , colorectal cancer , microbiology and biotechnology , regulation of gene expression , cancer research , antigen , cancer , linguistics , philosophy
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 ‐γ‐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 H LA‐CAT DNA constructs were also regulated in a locus‐specific fashion when assayed by in vitro functional assays using these human colorectal cell lines.