Intracellular localization and content of YB-1 protein in multidrug resistant tumor cells View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2006-02

AUTHORS

A. V. Vaiman, T. P. Stromskaya, E. Yu. Rybalkina, A. V. Sorokin, S. G. Guryanov, T. N. Zabotina, E. B. Mechetner, L. P. Ovchinnikov, A. A. Stavrovskaya

ABSTRACT

The multifunctional mammalian protein YB-1 is a member of the large DNA- and RNA-binding protein family with an evolutionarily ancient cold-shock domain. YB-1 is involved in multiple DNA- and mRNA-dependent events and regulates gene expression at various levels. It can be found both in the nucleus and the cytoplasm. Bound to DNA in the cell nucleus, YB-1 functions as a transcription factor interacting with inverted CCAAT-box (Y-box) in promoters and enhancers of multiple genes. In particular, YB-1 regulates activity of the multidrug resistance (MDR) genes MDR1 and LRP. In tumors, YB-1 has been suggested to be an early and global marker of MDR. In this study, we compared amounts of YB-1 mRNAs and intracellular localization of YB-1 protein in six pairs of drug sensitive and drug resistant sublines of diverse tumors. We have shown that neither great increase in the level of YB-1 mRNA nor substantial increase in the number of cells with nuclear localization of YB-1 are obligatory traits of drug resistant tumor cell populations. However, the cells with highest amounts of YB-1 mRNA also demonstrated increased quantities of MDR1, MRP1, BCRP, and LRP mRNAs encoding different MDR proteins. Transfection of two different populations of drug-sensitive cells with YB-1 cDNA led to increase in the amount of YB-1 mRNA. The quantities of MRP1 and LRP mRNAs increased in both populations. Introduction of YB-1 small hairpin RNA (shRNA) resulted in decreased amounts of YB-1 mRNA, as well as MRP1, LRP, and MDR1 mRNAs (in three different cell lines). Our data suggest that although YB-1 regulates several MDR genes, it could not be regarded as a global marker of already formed drug resistant tumor cell populations. It is most likely that at the first steps of MDR development YB-1 activity is necessary for propagation of resistant cell populations rather than for maintenance of drug resistance. More... »

PAGES

146-154

Identifiers

URI

http://scigraph.springernature.com/pub.10.1134/s0006297906020052

DOI

http://dx.doi.org/10.1134/s0006297906020052

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1003537932

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16489918


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