A C-ERBB-2 PROMOTER-SPECIFIC NUCLEAR MATRIX PROTEIN FROM HUMAN BREAST-TUMOR TISSUES MEDIATES NF-KAPPA-B DNA-BINDING ACTIVITY

The c-erbB-2 gene overexpression plays a major role in the pathogenesi s of breast cancer. Binding studies detected a nuclear matrix protein (NMP) in human breast tumor tissues that recognizes a matrix attachmen t re gion (MAR) in the immediate vicinity of the c-erbB-2 gene promote r. This NMP is expressed in breast tumor tissues and cell lines along with c-erbB-2, but is not found in corresponding normal tissues. Furth ermore, when NMP purified from the breast tumors by its affinity to th e MAR sequence is added to nuclear extracts of breast cancer cells, it selectively stimulates the binding of the NF-kappa B transcription fa ctor to DNA. A model is suggested in which the association of the MAR like sequence with the nuclear matrix raises the local concentration o f the specific NMP, which in turn interacts with the nuclear factor NF -kappa B to increase its local level. Such a complex could explain at a molecular level the ''increase in NF-kappa B DNA binding activity'' often observed in c-erbB-2- and BRCA1-positive human breast tumors. Th e increased NF-kappa B activity could thereby contribute to breast can cer progression.