c-fos and c-jun overexpression in malignant cells reduces their tumorigenic and metastatic potential, and affects their MHC class I gene expression.
Reduced co-expression of the c-fos and c-jun protooncogenes has been correlated with the down regulation of H-2K class I major histocompatibility antigens in high-metastatic cell lines from the Lewis lung carcinoma, B16 melanoma and the K1735 melanoma. Transfection of c-jun and c-fos genes into the high metastatic clones D122 (3LL) and F10.9 (B16 melanoma) resulted in activation of H-2 class I gene expression. D122 transfectants expressing high levels of c-jun and c-fos and F10.9 transfectants expressing high levels of c-fos exhibited markedly reduced tumorigenicity and were of low metastatic potential. In contrast, transfection of junB into the low metastatic, high H-2Kb, Db expressor clone A9 (3LL), reduced MHC class I gene expression, and converted the parental low, into high-metastatic cells. The data demonstrate the involvement of genes from the fos and jun family in regulation of MHC class I expression and consequently in regulation of immunogenicity and metastatic competence of tumor cells.
Yamit-Hezi
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Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Plaksin
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D
Eisenbach
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D000818:Animals; D001483:Base Sequence; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D005805:Genes, MHC Class I; D016762:Genes, fos; D016758:Genes, jun; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology*; D011485:Protein Binding; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation