Metformin affects alternative splicing of the estrogen receptor alpha gene in breast cancer cells

ABSTRACTMetformin ameliorates insulin resistance and reported to have prophylactic potential in breast cancer. The estrogen receptor-alpha gene is known to be alternatively spliced to the ER?46 isoform with decreased expression in tamoxifen-resistant breast cancer cells. We show here that metformin had a differential effect on its alternative splicing in MCF-7 and its tamoxifen-resistant derivative, TAMR1 cells. Metformin altered the tamoxifen-induced expression of ER?46 and treatment of cell-transplanted nude mice showed decreased tumor weight only in TAMR1 cell tumors. This is the first report to show metformin specifically involved in alternative splicing of genes in breast cancer cells. Keywords: Estrogen receptor-alpha (ER?), estrogen, tamoxifen, metformin