A c-erbB-2 promoter-specific nuclear matrix protein from human breast tumor tissues mediates NF-kappaB 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 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.
Raziuddin
A
A
Intramural Research Support Program, Science Application International Corporation/Frederick, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA.
Court
D
D
Sarkar
F H
FH
Liu
Y L
YL
Kung
H f
Hf
Raziuddin
R
R
D034961:Antigens, Nuclear; D001665:Binding Sites; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004926:Escherichia coli; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016328:NF-kappa B / Q000235:genetics*; D009687:Nuclear Proteins / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*
D034961:Antigens, Nuclear; D004247:DNA; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases