Upregulation of nuclear transporter, Kpnβ1, contributes to accelerated cell proliferation- and cell adhesion-mediated drug resistance (CAM-DR) in diffuse large B-cell lymphoma

Background The Karyopherin proteins are involved in the shuttling of cargo proteins, and certain RNAs, across the nuclear pore complex into and out of the cell nucleus. Karyopherin beta 1 (Kpn beta 1) is a member of the Karyopherin beta superfamily of nuclear transport proteins. In addition to the nuclear import function, Kpn beta 1 is associated with the occurrence of tumors. This study investigated the expression and biologic function of Kpn beta 1 in diffuse large B-cell lymphoma (DLBCL). Methods The prognostic value of Kpn beta 1 expression was evaluated using immunohistochemical staining. The role of Kpn beta 1 on cell proliferation- and cell adhesion-mediated drug resistance (CAM-DR) was also determined. Results We demonstrated that Kpn beta 1 mRNA and protein expression levels were significantly higher in DLBCL B-cells and DLBCL cell lines than in normal CD19 purified B-cells. Immunohistochemical analysis suggested that the expression of Kpn beta 1 was correlated with Ki-67 (P < 0.001). Kaplan-Meier curve showed that high expression of Kpn beta 1 was significantly associated with shorter overall survival. In addition, Kpn beta 1 was associated with the proliferation of DLBCL cells. Importantly, we found that Kpn beta 1 could interact with p65 and promote CAM-DR via accelerating NF-kappa B activation in DLBCL. Conclusions Patients with tumors highly expressing Kpn beta 1 have poorer overall survivals. Kpn beta 1 interacts with p65 and enhances CAM-DR.