Promotion of tumor growth by transfecting antisense DNA to suppress endogenous H-2Kk MHC gene expression in AKR mouse thymoma.
Many AKR spontaneous thymomas are reported to express different amounts of the major histocompatibility complex class I H-2Kk molecules. Moreover, H-2Kk-deficient AKR tumor cells are found to be more malignant when compared to tumor cells that express abundant levels of the H-2Kk molecules. To corroborate further the role of H-2Kk in tumorigenesis of AKR leukemia, we have, in this study, expressed antisense H-2Kk RNA in a high-H-2Kk-expressing and poorly tumorigenic AKR thymoma cell line 369. The down-regulation of H-2Kk molecules in the transfected 369 clones rendered them more tumorigenic in syngeneic AKR/J mice. The increase in oncogenicity correlates well with a concomitant reduction in their susceptibility to tumor-specific cytotoxic T lymphocytes in vitro. These results suggest the relevance of H-2Kk molecules in the immune surveillance of AKR tumors.
Hui
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KM
Institute of Molecular and Cell Biology, National University of Singapore, Kent Ridge.
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Foo
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Oei
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D000818:Animals; D002999:Clone Cells; D016373:DNA, Antisense / Q000235:genetics*; D015536:Down-Regulation; D015870:Gene Expression; D006183:H-2 Antigens / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D007370:Interferon Type I / Q000494:pharmacology; D051379:Mice; D008806:Mice, Inbred AKR; D016372:RNA, Antisense / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013945:Thymoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D013953:Thymus Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D014162:Transfection
D016373:DNA, Antisense; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D007370:Interferon Type I; D016372:RNA, Antisense