Upregulation of nuclear transporter, Kpnß1, contributes to accelerated cell proliferation- and cell adhesion-mediated drug resistance (CAM-DR) in diffuse large B-cell lymphoma.

ABSTRACT

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 ß1 (Kpnß1) is a member of the Karyopherin ß superfamily of nuclear transport proteins. In addition to the nuclear import function, Kpnß1 is associated with the occurrence of tumors. This study investigated the expression and biologic function of Kpnß1 in diffuse large B-cell lymphoma (DLBCL). METHODS: The prognostic value of Kpnß1 expression was evaluated using immunohistochemical staining. The role of Kpnß1 on cell proliferation- and cell adhesion-mediated drug resistance (CAM-DR) was also determined. RESULTS: We demonstrated that Kpnß1 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 Kpnß1 was correlated with Ki-67 (P < 0.001). Kaplan-Meier curve showed that high expression of Kpnß1 was significantly associated with shorter overall survival. In addition, Kpnß1 was associated with the proliferation of DLBCL cells. Importantly, we found that Kpnß1 could interact with p65 and promote CAM-DR via accelerating NF-κB activation in DLBCL. CONCLUSIONS: Patients with tumors highly expressing Kpnß1 have poorer overall survivals. Kpnß1 interacts with p65 and enhances CAM-DR.