A c-erbB-2 promoter-specific nuclear matrix protein from human breast tumor tissues mediates NF-kappaB DNA binding activity.

The Journal of Biological Chemistry
RaziuddinR Raziuddin

Abstract

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 region (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-kappaB 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-kappaB to increase its local level. Such a complex could explain at a molecular level the "increase in NF-kappaB DNA binding activity" often observed in c-erbB-2- and BRCA1-positive human breast tumors. The increased NF-kappaB activity could thereby contribute to breast cancer progression.

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Citations

Jul 4, 2002·Cell Biology International·Aleksandra UskokovićGoran Poznanović
Sep 6, 2002·Experimental Gerontology·Oriana TrubianiRoberto Di Primio
Jan 10, 2001·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·P ThunyakitpisalJ P Bidwell
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Aug 30, 2000·The Journal of Biological Chemistry·K WuF J Couch

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