c-erbB-2 promoter-specific DNA-binding protein isolated from human breast cancer tissues displays mitogenic activity.
Amplification and overexpression of the c-erbB-2 gene appears to play a role in the pathogenesis of human breast and other cancers. Frequent amplification (20-30%) of the c-erbB-2 gene was observed in human adenocarcinomas of kidney, pancreas, lung, ovarian, and breast cancer. The gene product is a 185-kDa glycoprotein that has intrinsic tyrosine kinase activity and is believed to be a receptor. Several candidate ligands have been described. In the present study we have identified and purified a novel DNA-binding protein from malignant human breast tissues. The protein binds to a core element (-22 to +9, +1 being the transcription start site) of the c-erbB-2 promoter region in a sequence-specific manner. The affinity-purified protein has the ability to induce DNA synthesis in quiescent NIH/3T3 cells, suggesting that the factor has mitogenic activity. The purified protein induces c-erbB-2 expression on the surface of microinjected NIH/3T3 cells. This DNA-binding protein is a sequence-specific cellular factor that is associated with high level expression of the c-erbB-2 gene and appears to play a role in cell transformation. Understanding the control and expression of this DNA-binding protein may shed light on the mechanism(s) of c-erbB-2 gene regulation and its potential role in the pathogenesis of human adenocarcinomas.
Sarkar
F H
FH
Department of Pathology, Wayne State University Medical School, Detroit, Michigan 48201.
Smith
M R
MR
Hoover
T
T
Princler
G
G
Crissman
J D
JD
Visscher
D W
DW
Longo
D L
DL
Kung
H F
HF
Raziuddin
D016475:3T3 Cells; D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D001943:Breast Neoplasms / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology*; D002460:Cell Line; D002846:Chromatography, Affinity; D004247:DNA / Q000096:biosynthesis* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D066246:ErbB Receptors / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000378:metabolism*; D011519:Proto-Oncogenes; D018719:Erb-b2 Receptor Tyrosine Kinases; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured
D004247:DNA; D004268:DNA-Binding Proteins; D066246:ErbB Receptors; D009838:Oligodeoxyribonucleotides; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases