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 show n in roughly 30% of breast cancer patients, Increased levels of HER2/n eu mRNA in some breast cancer cell lines is partially caused by increa sed gene transcription, In MDA-MB453 human breast cancer cells, an act ivated 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 app roximately 110, 70, and 35 kD interact with this DNA element, This reg ion of the human HER2/neu promoter is highly conserved in the rat and mouse promoters and was shown to be capable of mediating transcription al trans-activation in HER2/neu-overexpressing MDA-MB453 cells while h aving little effect in a control cell line that expresses basal levels of HER2/neu, Knowledge on interactions between this DNA element and n uclear protein factors may help us better understand the molecular mec hanisms regulating HER2/neu overexpression in breast cancer cells.