Rybalkina E Iu, Stromskaia T P, Ovchinnikov L P, Stavrovskaia A A
Vopr Onkol. 2013;59(5):623-8.
In this study, we investigated how the protein YB-1 influenced on the expression of genes coding ABC transporters and on drug resistance in several cell lines, in which originally gene MDR1, coding P-glycoprotein, was not expressed. These populations were significantly different in the presence of mRNA YB-1 and the nature of the intracellular localization of the protein YB-1. However incubation of cells in all studied populations in the culture medium with serum after starvation led to translocation of YB-1 in the cell nucleus. The increase of the number of cells with nuclear localization of YB-1 correlated with increased amount of mRNA YB-1. Processing of cells with drug LY-294,002 by PI3K/Akt inhibitor prevented the translocation of the protein YB-1 into the nuclei of cells, and the cells became more sensitive to the toxic action. Thus, we observed that the signaling pathways involved in control of cell proliferation, in particular a signaling cascade PI3K/Akt were involved in the control of the intracellular localization of YB-1 in cell populations of ovarian cancer, melanoma and human prostate cancer. In these cells the nuclear localization of YB-1 correlated with an expression of MDR and MRP1 DCRP genes and with a sensitivity of cells to a number of drugs.
在本研究中，我们调查了蛋白质YB-1如何影响编码ABC转运蛋白的基因表达以及几种细胞系中的耐药性，这些细胞系最初不表达编码P-糖蛋白的基因MDR1。这些细胞群体在mRNA YB-1的存在以及蛋白质YB-1的细胞内定位性质方面存在显著差异。然而，饥饿后在含血清的培养基中培养所有研究的细胞群体，导致YB-1易位至细胞核。YB-1核定位的细胞数量增加与mRNA YB-1量的增加相关。用PI3K/Akt抑制剂LY-294,002处理细胞可阻止蛋白质YB-1易位至细胞核，并且细胞对毒性作用变得更敏感。因此，我们观察到参与细胞增殖控制的信号通路，特别是信号级联PI3K/Akt，参与了卵巢癌、黑色素瘤和人类前列腺癌细胞群体中YB-1的细胞内定位控制。在这些细胞中，YB-1的核定位与MDR和MRP1 DCRP基因的表达以及细胞对多种药物的敏感性相关。
