Regulation of major histocompatibility complex class I expression by NF-κB-related proteins in breast cancer cells

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 kappa B site or on a longer promoter is transactivated by NF-kappa B complexes containing p65 or RelB. p100 as well as I kappa B-alpha 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-gamma or TNF-alpha. Stable transfection of a unresponsive mutated I kappa B-alpha Ser 32-36 expression 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-kappa B activation.