YB-1 Protein and Multidrug Resistance of Tumor Cells

Y-box binding protein 1 (YB-1) is a member of the large protein family with an evolutionarily ancient cold-shock domain. It is involved in the regulation of some global traits of malignancy and functions both in the cell nucleus and cytoplasm. We investigated the content of YB-1 mRNA and proportion of cells with YB-1 nuclear localization in breast cancer (BC) tumors taken at mastectomy. We showed that an increased level of YB-1 mRNA in samples correlated with tumor aggressiveness and increased expression of multidrug resistance (MDR) genes. Over-expression of several MDR genes was found in the samples with high YB-1 mRNA content and with YB-1 cytoplasmic localization. This suggests that YB-1 regulates expression of some MDR genes at the level of cytoplasm. The nuclear YB-1 localization also correlated with BC aggressiveness; however, these interconnections were less prominent in comparison with those between a high YB-1 mRNA content and the mentioned tumor characteristics. Our results show that neo-adjuvant chemotherapy induces translocation of YB-1 from the cytoplasm to the cell nucleus in mammary tumors. In the experiments with cell cultures we showed that chemotherapeutic drugs stimulated YB-1 nuclear translocation, as well as MDR genes expression and cell multidrug resistance. We suppose that YB-1 nuclear translocation determines adaptation of tumor cell populations to the environmental impact, while a high YB-1 mRNA content is an intrinsic feature that contributes to the control of the global traits of malignancy. A combination YB-1 mRNA content and its intracellular localization may serve as a test for BC prognosis.