PMID- 26498772 OWN - NLM STAT- MEDLINE DCOM- 20160629 LR - 20220408 IS - 1432-1335 (Electronic) IS - 0171-5216 (Linking) VI - 142 IP - 3 DP - 2016 Mar TI - Upregulation of nuclear transporter, Kpnbeta1, contributes to accelerated cell proliferation- and cell adhesion-mediated drug resistance (CAM-DR) in diffuse large B-cell lymphoma. PG - 561-72 LID - 10.1007/s00432-015-2057-4 [doi] AB - 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 beta1 (Kpnbeta1) is a member of the Karyopherin beta superfamily of nuclear transport proteins. In addition to the nuclear import function, Kpnbeta1 is associated with the occurrence of tumors. This study investigated the expression and biologic function of Kpnbeta1 in diffuse large B-cell lymphoma (DLBCL). METHODS: The prognostic value of Kpnbeta1 expression was evaluated using immunohistochemical staining. The role of Kpnbeta1 on cell proliferation- and cell adhesion-mediated drug resistance (CAM-DR) was also determined. RESULTS: We demonstrated that Kpnbeta1 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 Kpnbeta1 was correlated with Ki-67 (P < 0.001). Kaplan-Meier curve showed that high expression of Kpnbeta1 was significantly associated with shorter overall survival. In addition, Kpnbeta1 was associated with the proliferation of DLBCL cells. Importantly, we found that Kpnbeta1 could interact with p65 and promote CAM-DR via accelerating NF-kappaB activation in DLBCL. CONCLUSIONS: Patients with tumors highly expressing Kpnbeta1 have poorer overall survivals. Kpnbeta1 interacts with p65 and enhances CAM-DR. FAU - He, Song AU - He S AD - Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China. FAU - Miao, Xiaobing AU - Miao X AD - Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China. FAU - Wu, Yaxun AU - Wu Y AD - Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China. FAU - Zhu, Xinghua AU - Zhu X AD - Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China. FAU - Miao, Xianjing AU - Miao X AD - Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, Jiangsu, China. FAU - Yin, Haibing AU - Yin H AD - Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China. FAU - He, Yunhua AU - He Y AD - Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, Jiangsu, China. FAU - Li, Chunsun AU - Li C AD - Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China. FAU - Liu, Yushan AU - Liu Y AD - Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China. FAU - Lu, Xiaoyun AU - Lu X AD - Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China. FAU - Chen, Yali AU - Chen Y AD - Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China. FAU - Wang, Yuchan AU - Wang Y AD - Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, Jiangsu, China. wangyuchannt@126.com. FAU - Xu, Xiaohong AU - Xu X AD - Department of Oncology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China. xuxiaohongnantong@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151023 PL - Germany TA - J Cancer Res Clin Oncol JT - Journal of cancer research and clinical oncology JID - 7902060 RN - 0 (KPNB1 protein, human) RN - 0 (beta Karyopherins) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Cell Adhesion/genetics MH - Cell Line, Tumor MH - Cell Proliferation/*genetics MH - Drug Resistance, Neoplasm/*genetics MH - Female MH - *Gene Expression Regulation, Neoplastic MH - Humans MH - Lymphoma, Large B-Cell, Diffuse/*genetics/metabolism/mortality/pathology MH - Male MH - Middle Aged MH - Up-Regulation MH - beta Karyopherins/*genetics/metabolism OTO - NOTNLM OT - Cell adhesion-mediated drug resistance (CAM-DR) OT - Diffuse large B-cell lymphoma (DLBCL) OT - Kpnbeta1 OT - NF-kappaB p65 OT - Proliferation EDAT- 2015/10/27 06:00 MHDA- 2016/06/30 06:00 CRDT- 2015/10/27 06:00 PHST- 2015/05/17 00:00 [received] PHST- 2015/10/13 00:00 [accepted] PHST- 2015/10/27 06:00 [entrez] PHST- 2015/10/27 06:00 [pubmed] PHST- 2016/06/30 06:00 [medline] AID - 10.1007/s00432-015-2057-4 [pii] AID - 10.1007/s00432-015-2057-4 [doi] PST - ppublish SO - J Cancer Res Clin Oncol. 2016 Mar;142(3):561-72. doi: 10.1007/s00432-015-2057-4. Epub 2015 Oct 23.