[Back to Issue 2 ToC] [Back to Journal Contents] [Back to Biochemistry (Moscow) Home page]

Intracellular Localization and Content of YB-1 Protein in Multidrug Resistant Tumor Cells

A. V. Vaiman1, T. P. Stromskaya1, E. Yu. Rybalkina1, A. V. Sorokin2, S. G. Guryanov2, T. N. Zabotina1, E. B. Mechetner3, L. P. Ovchinnikov2, and A. A. Stavrovskaya1*

1Institute of Carcinogenesis, Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, Kashirskoe Shosse 24, 115478 Moscow, Russia; E-mail: vaiman@yandex.ru

2Institute of Protein Research, Russian Academy of Sciences, 142290 Pushchino, Moscow Region, Russia; fax: (7-495) 632-7871; E-mail: ovchinn@vega.protres.ru

3Chemicon International, Inc., 28820 Single Oak Drive, Temecula, CA 92590, USA; E-mail: emechetner@cox.net

* To whom correspondence should be addressed.

Received July 16, 2005; Revision received October 6, 2005
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.
KEY WORDS: YB-1 protein, mRNA, tumor cell, multidrug resistance, resistant cell, protein localization

DOI: 10.1134/S0006297906020052