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 c orrelated with the down regulation of H-2K class I major histocompatib ility antigens in high-metastatic cell lines from the Lewis lung carci noma, 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 m elanoma) resulted in activation of H-2 class I gene expression. D122 t ransfectants expressing high levels of c-jun and c-fos and F10.9 trans fectants expressing high levels of c-fos exhibited markedly reduced tu morigenicity and were of low metastatic potential. In contrast, transf ection of junB into the low metastatic, high H-2K(b), D(b) expressor c lone A9 (3LL), reduced MHC class I gene expression, and converted the parental low, into high-metastatic cells. The data demonstrate the inv olvement of genes from the fos and jun family in regulation of MHC cla ss I expression and consequently in regulation of immunogenicity and m etastatic competence of tumor cells.