Lei Bin, Qi Wenjuan, Zhao Yunfei, Li Yumei, Liu Shuguang, Xu Xiaoyan, Zhi Chen, Wan Liyan, Shen Hong
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China.
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China.
Hum Pathol. 2015 Feb;46(2):217-24. doi: 10.1016/j.humpath.2014.07.026. Epub 2014 Oct 30.
The PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) is highly expressed in many types of tumors. However, its role in lung adenocarcinoma remains elusive. The aims of this study were to investigate the correlation between PBK/TOPK and mutant p53 in lung adenocarcinoma and to evaluate the effect of PBK/TOPK on cell proliferation and viability. Expression of PBK/TOPK and mutant p53 was detected in 127 cases of lung adenocarcinoma and was examined in the A549, GLC-82, and H358 lung adenocarcinoma cell lines by immunohistochemistry staining and Western blot assay. When PBK/TOPK expression was down-regulated by TOPK-specific siRNA in the A549 and GLC-82 lines, the effects of PBK/TOPK on cell proliferation, viability, and mutant p53 expression were evaluated. Expression of PBK/TOPK correlated positively with mutant p53 in both tumor tissues and cell lines. Kaplan-Meier survival analysis demonstrated that PBK/TOPK, mutant p53, lymph node metastasis, distant metastasis, high TNM stage, and poor tumor differentiation were associated with a poor prognosis. Cox multivariate analysis showed that PBK/TOPK, mutant p53, lymph node metastasis, and distant metastasis could each serve as an independent prognostic factor. After down-regulation of PBK/TOPK in the A549 and GLC-82 cell lines, mutant p53 expression was decreased, and cell proliferation and viability were significantly inhibited. Therefore, our results suggest that PBK/TOPK correlates with mutant p53 and affects cell proliferation and viability as well as prognosis in lung adenocarcinoma.
PDZ结合激酶/T-LAK细胞源蛋白激酶（PBK/TOPK）在多种肿瘤中高表达。然而，其在肺腺癌中的作用仍不清楚。本研究旨在探讨肺腺癌中PBK/TOPK与突变型p53之间的相关性，并评估PBK/TOPK对细胞增殖和活力的影响。通过免疫组织化学染色和蛋白质印迹分析检测了127例肺腺癌中PBK/TOPK和突变型p53的表达，并在A549、GLC-82和H358肺腺癌细胞系中进行了检测。当用TOPK特异性siRNA下调A549和GLC-82细胞系中PBK/TOPK的表达时，评估了PBK/TOPK对细胞增殖、活力和突变型p53表达的影响。在肿瘤组织和细胞系中，PBK/TOPK的表达均与突变型p53呈正相关。Kaplan-Meier生存分析表明，PBK/TOPK、突变型p53、淋巴结转移、远处转移、高TNM分期和肿瘤低分化与预后不良相关。Cox多因素分析显示，PBK/TOPK、突变型p53、淋巴结转移和远处转移均可作为独立的预后因素。在A549和GLC-82细胞系中下调PBK/TOPK后，突变型p53表达降低，细胞增殖和活力受到显著抑制。因此，我们的结果表明，PBK/TOPK与突变型p53相关，并影响肺腺癌的细胞增殖、活力及预后。
