Downregulation of MHC Class I antigens has been observed in many cancers and usually results from a decreased gene transcription. A reporter CAT gene dependent on the MHC Class I κB site or on a longer promoter is transactivated by NF-κB complexes containing p65 or RelB. p100 as well as IκB-α are potent inhibitors of this transcription 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 induced by stimulation with the cytokines IFN-γ or TNF-α. Stable transfection of a unresponsive mutated IκB-α Ser 32-36 expression vector showed that TNF-α induced MHC Cl I expression in an NF-κB-dependent way while IFN-γ did it independently of any NF-κB activation.