క్యాన్సర్ సైన్స్ & థెరపీ

Tumor Specific Oligomeric Forms of Nucleophosmin

Abstract

Natalia M Vladimirova, Maria A Pisareva, Oksana O Zharskaya, Natalia L Deineko, Tatiana I Bulycheva and Olga M Volpina

Background: According to recent data malignization of cells is accompanied not only by overexpression of protein B23/nucleophosmin, but also by formation of its new structural forms including unusual oligomers. The aim of this study was to evaluate the structural features of nucleophosmin in tumor cells. Materials and methods: Structural state of nucleophosmin was analyzed in different human tumor cells (HeLa, NGP, Hep G2, Osa-CL, Jurkat, Ramos, K-562) and human lymphocytes stimulated to proliferate by phytohemagglutinin. Commercially available monoclonal antibodies and new obtained by us antipeptide antibodies were used for analysis of monomer-oligomer state of nucleophosmin by immunochemical method and for determination of intracellular localization of monomers and oligomers by immunocytochemical method. Results: We revealed unusual SDS-resistant oligomeric forms of nucleophosmin in tumor cells of different type. Using protein chemistry strategy we showed the presence of truncated B23 isoforms in HeLa cells and their ability to form SDS-resistant oligomers. For the first time we created antipeptide antibodies which allowed differentiate monomeric and oligomeric nucleophosmin forms in tumor cells. Using these antibodies we showed different intracellular localization of monomers and oligomers in tumor cells. Conclusions: We propose that formation of SDS-resistant oligomeric forms of nucleophosmin is a common feature of human tumor cells and their detection with described antipeptide antibodies may be used for tumor diagnostics.