A limited number of studies are devoted to regulating TRIP6 expression in cancer. Hence, we aimed to unveil the regulation of TRIP6 expression in MCF-7 breast cancer cells (with high TRIP6 expression) and taxane-resistant MCF-7 sublines (manifesting even higher TRIP6 expression). We found that TRIP6 transcription is regulated primarily by the cyclic AMP response element (CRE) in hypomethylated proximal promoters in both taxane-sensitive and taxane-resistant MCF-7 cells. Furthermore, in taxane-resistant MCF-7 sublines, TRIP6 co-amplification with the neighboring ABCB1 gene, as witnessed by fluorescence in situ hybridization (FISH), led to TRIP6 overexpression. Ultimately, we found high TRIP6 mRNA levels in progesterone receptor-positive breast cancer and samples resected from premenopausal women.

Department of Biochemistry Cell and Molecular Biology 3rd Faculty of Medicine Charles University 100 00 Prague Czech Republic

Department of Cancer Genetics Institute for Cancer Research Oslo University Hospital 0310 Oslo Norway

Department of Cell Biology Faculty of Science Charles University 128 00 Prague Czech Republic

Department of Chemistry Institute of Chemical Biology and Drug Discovery Stony Brook University State University of New York Stony Brook NY 11794 USA

Department of Cytogenetics Institute of Hematology and Blood Transfusion 128 00 Prague Czech Republic

Department of Medical Genetics Institute of Clinical Medicine Faculty of Medicine University of Oslo 0424 Oslo Norway

Laboratory of Pharmacogenomics Biomedical Center Faculty of Medicine Charles University 323 00 Pilsen Czech Republic

Toxicogenomics Unit National Institute of Public Health 100 00 Prague Czech Republic

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