Disruption of Estrogen Signaling Enhances Invasiveness of Breast Cancer Cells by Attenuating a HER2-independent Gene Repression Program

Disruption of Estrogen Signaling Enhances Invasiveness of Breast Cancer Cells by Attenuating a HER2-independent Gene Repression Program In ER+ breast cancer cells, genes that were directly or indirectly repressed by E2, but not E2-activated genes, overlapped the gene overexpression signature of clinical progression of ductal carcinoma in situ to invasive ductal carcinoma. They also showed a strong collective functional bias toward tumor progression. In MCF-7 (ER+/PR+), ZR-75-1 (ER+/PR+) and BT474 (ER+/PR+/HER2 amplified) cells hormone depletion or tamoxifen treatment restored gene expression and invasiveness that were inhibited by E2.