Modeling breast cell cycle regulation - overcoming drug resistance

In breast cancer treatment for many cases intrinsic or acquired resistance against available therapeutics leads to death. According to the present biological understanding, drug resistance is caused by molecular mechanisms in the complex network of proteins that regulate cell proliferation by activation of the estrogen receptor (ER), hereby allowing the cell to bypass the classical estrogen receptor signalling pathway after inhibition of the ER. Target proteins for this study were chosen according to the present understanding of estrogen receptor based cell cycle control, including proteins from genomic and non genomic ER-dependant pathways, as well as from ER-independent signalling events. We used MCF7 cells (ATCC, HTB-22), to generate a Tamoxifen-resistant cell line out of this parental strain. The assay is based on upregulation of genes during Tamoxifen treatment, which allows the cells to proliferate in presence of Tamoxifen