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PBK/TOPK expression correlates with mutant p53 and affects patients' prognosis and cell proliferation and viability in lung adenocarcinoma.

Abstract
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.
AuthorsBin Lei, Wenjuan Qi, Yunfei Zhao, Yumei Li, Shuguang Liu, Xiaoyan Xu, Chen Zhi, Liyan Wan, Hong Shen
JournalHuman pathology (Hum Pathol) Vol. 46 Issue 2 Pg. 217-24 (Feb 2015) ISSN: 1532-8392 [Electronic] United States
PMID25466965 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier Inc. All rights reserved.
Chemical References
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Mitogen-Activated Protein Kinase Kinases
  • PDZ-binding kinase
Topics
  • Adenocarcinoma (diagnosis, genetics, metabolism)
  • Adenocarcinoma of Lung
  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Cycle (physiology)
  • Cell Differentiation (genetics, physiology)
  • Cell Line, Tumor
  • Cell Proliferation (physiology)
  • Cell Survival
  • Female
  • Humans
  • Lung Neoplasms (diagnosis, genetics, metabolism)
  • Male
  • Middle Aged
  • Mitogen-Activated Protein Kinase Kinases (genetics, metabolism)
  • Neoplasm Staging
  • Prognosis
  • Tumor Suppressor Protein p53 (genetics, metabolism)

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