REGULATION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I EXPRESSION BY NF-KAPPA-B-RELATED PROTEINS IN BREAST-CANCER CELLS

Downregulation of MHC Class I antigens has been observed in many cance rs and usually results from a decreased gene transcription. A reporter CAT gene dependent on the MHC Class I kappa B site or on a longer pro moter is transactivated by NF-kappa B complexes containing p65 or RelB . p100 as well as I kappa B-alpha are potent inhibitors of this transc ription and p100 sequesters RelB and p65 complexes in the cytoplasm of breast cancer cells. However, although p100 is highly expressed in a number of breast cancer cell lines, MHC Class I antigen expression was observed on all the cell lines we analysed and could be further induc ed by stimulation with the cytokines IFN-gamma or TNF-alpha. Stable tr ansfection of a unresponsive mutated I kappa B-alpha Ser 32-36 express ion vector showed that TNF-alpha induced MHC Cl I expression in an NF- kappa B-dependent way while IFN-gamma did it independently of any NF-k appa B activation.