Identification of a specific DNA region required for enhanced transcription of HER2/neu in the MDA-MB453 breast cancer cell line.
Overexpression and/or amplification of the HER2/neu gene has been shown in roughly 30% of breast cancer patients. Increased levels of HER2/neu mRNA in some breast cancer cell lines is partially caused by increased gene transcription. In MDA-MB453 human breast cancer cells, an activated trans-acting factor is involved in the increased transcription of HER2/neu by mediating its effects through a specific DNA region in the HER2/neu promoter. A methylation interference experiment showed a novel sequence for protein-DNA interactions. Three polypeptides of approximately 110, 70, and 35 kD interact with this DNA element. This region of the human HER2/neu promoter is highly conserved in the rat and mouse promoters and was shown to be capable of mediating transcriptional trans-activation in HER2/neu-overexpressing MDA-MB453 cells while having little effect in a control cell line that expresses basal levels of HER2/neu. Knowledge on interactions between this DNA element and nuclear protein factors may help us better understand the molecular mechanisms regulating HER2/neu overexpression in breast cancer cells.
Miller
S J
SJ
Department of Tumor Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Xing
X
X
Xi
L
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Hung
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MC
D000818:Animals; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D017124:Conserved Sequence; D004247:DNA / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D051381:Rats; D017422:Sequence Analysis, DNA; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D004247:DNA