Identification of a Specific DNA Region Required for Enhanced Transcription of HER2/neuin the MDA-MB453 Breast Cancer Cell Line

摘要

ABSTRACTOverexpression and/or amplification of the HER2/neugene has been shown in roughly 30 of breast cancer patients. Increased levels of HER2/neumRNA in some breast cancer cell lines is partially caused by increased gene transcription. In MDA-MB453 human breast cancer cells, an activatedtrans-acting factor is involved in the increased transcription of HER2/neuby mediating its effects through a specific DNA region in the HER2/neupromoter. 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/neupromoter is highly conserved in the rat and mouse promoters and was shown to be capable of mediating transcriptionaltrans-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/neuoverexpression in breast cancer cell