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 pathogenesis of breast cancer. Binding studies detected a nuclear matrix protein (NMP) in human breast tumor tissues that recognizes a matrix attachment re gion (MAR) in the immediate vicinity of the c-erbB-2 gene promoter. This NMP is expressed in breast tumor tissues and cell lines along with c-erbB-2, but is not found in corresponding normal tissues. Furthermore, when NMP purified from the breast tumors by its affinity to the MAR sequence is added to nuclear extracts of breast cancer cells, it selectively stimulates the binding of the NF-kappa B transcription factor to DNA. A model is suggested in which the association of the MAR like sequence with the nuclear matrix raises the local concentration of 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. The increased NF-kappa B activity could thereby contribute to breast cancer progression. [References: 45]

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