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.