Connection of intracellular protein YB-1 localization in cell cultures of human tumors with multidrug resistance

• Published in: Voprosy onkologij Vol. 59; no. 5; p. 623
• Main Authors: Rybalkina, E Iu, Stromskaia, T P, Ovchinnikov, L P, Stavrovskaia, A A
• Format: Journal Article
• Language: Russian
• Published: Russia (Federation) 2013
• Subjects: Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; ATP Binding Cassette Transporter, Sub-Family B; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism; Cell Line, Tumor; Cell Proliferation - drug effects; Chromones - pharmacology; Chromones - therapeutic use; Doxorubicin - pharmacology; Drug Resistance, Multiple - drug effects; Drug Resistance, Neoplasm - drug effects; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - therapeutic use; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Male; Melanoma - drug therapy; Melanoma - metabolism; Morpholines - pharmacology; Morpholines - therapeutic use; Neoplasms - drug therapy; Neoplasms - metabolism; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - metabolism; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; RNA, Messenger - metabolism; Signal Transduction - drug effects; Skin Neoplasms - drug therapy; Skin Neoplasms - metabolism; Vinblastine - pharmacology; Y-Box-Binding Protein 1 - genetics; Y-Box-Binding Protein 1 - metabolism
• ISSN: 0507-3758

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.