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.