Highly-expressed p100/p52 (NFKB2) sequesters other NF-kappa B-related proteins in the cytoplasm of human breast cancer cells.
Several observations have suggested that NF-kappa B transcription factors could be involved in carcinogenesis. To investigate the possibility that members of the NF-kappa B family participate in the molecular control of the transformed phenotype, we examined the expression of these proteins in human breast cancer cell lines as well as in primary tumors. Western Immunoblots demonstrated high expression of the p52 precursor p100 (NFKB2) in several breast cancer cell lines while human mammary epithelial cells express this protein only faintly. Eighteen primary breast tumors out of 24 displayed significant expression of the p100/p52 protein. In MDA-MB-435 cells, overexpressed p100 and p52 are predominantly cytoplasmic and coimmunoprecipitation experiments demonstrated that p100 sequesters the heterodimer p50/p65 in the cytoplasm. We demonstrate that most p65 protein is complexed with p100 in these cells while it is complexed predominantly with I kappa B-alpha in cell lines expressing less p100. Our data strengthen the hypothesis that NF-kappa B could be involved in carcinogenesis and suggest that the p100/p52 NF-kappa B subunit could play a role in the development of human breast cancers, possibly by sequestering other NF-kappa B-related proteins in the cytoplasm.
D000230:Adenocarcinoma / Q000378:metabolism*; D000911:Antibodies, Monoclonal; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D004848:Epithelium / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D015151:Immunoblotting; D046911:Macromolecular Substances; D008970:Molecular Weight; D016328:NF-kappa B / Q000032:analysis / Q000096:biosynthesis* / Q000737:chemistry; D052003:NF-kappa B p52 Subunit; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000737:chemistry; D012016:Reference Values; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D046911:Macromolecular Substances; D016328:NF-kappa B; D052003:NF-kappa B p52 Subunit; D011518:Proto-Oncogene Proteins