Regulation of major histocompatibility complex class I expression by NF-kappaB-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 kappaB site or on a longer promoter is transactivated by NF-kappaB complexes containing p65 or RelB. p100 as well as IkappaB-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 IkappaB-alpha Ser 32-36 expression vector showed that TNF-alpha induced MHC Cl I expression in an NF-kappaB-dependent way while IFN-gamma did it independently of any NF-kappaB activation.
Laboratory of Medical Chemistry/Medical Oncology, Institut Gustave Roussy, Villejuif, France.
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E
Dejardin
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V
Deregowski
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R
Greimers
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Z
Cai
S
S
Chouaib
M P
MP
Merville
V
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Bours
D000970:Antineoplastic Agents / Q000494:pharmacology; D001665:Binding Sites / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D015395:Histocompatibility Antigens Class I / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins; D007371:Interferon-gamma / Q000494:pharmacology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins / Q000235:genetics; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D015395:Histocompatibility Antigens Class I; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D011518:Proto-Oncogene Proteins; C497593:RELB protein, human; D011994:Recombinant Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D051841:Transcription Factor RelB; D007371:Interferon-gamma