Overexpression of PDZ-binding kinase confers malignant phenotype in prostate cancer via the regulation of E2F1.

Abstract

Roles and mechanisms of cell cycle-specific transcription factor E2F1 on prostate cancer (PCa) have not been fully elucidated. To address this problem, we here identified PDZ-binding kinase (PBK) as a direct target for E2F1 through bioinformatics binding site prediction, combined with chromatin immunoprecipitation-PCR (ChIP-PCR), quantitative (Q)-PCR and Western blot analysis. Then, we observed that the knockdown of both E2F1 and PBK could suppress cell proliferation, invasion and migration of PCa cell lines in vitro. Based on Taylor dataset, we found that PBK upregulation occurred more frequently in PCa patients with the older age of patients (P=0.044), the higher Gleason score (P<0.001), the advanced clinical pathological stage (P=0.019), the presence of metastasis (P=0.008), the overall survival (P<0.001) and PSA failure (P=0.004). More interestingly, the survival analysis identified PBK as an independent factor for predicting the biochemical recurrence-free survival of PCa patients (P=0.041). Taken together, these findings offer the convincing evidence for the first time that the overexpression of PBK may lead to high malignant phenotype in PCa cells via the regulation of E2F1. PBK may function as a biomarker that can differentiate patients with biochemical recurrent and non-biochemical recurrent disease following radical prostatectomy, highlighting its potential as a therapeutic target.

• Authors: Jia-Hong Chen, Yu-Xiang Liang, Hui-Chan He, Jin-Yan Chen, Jian-Ming Lu, Guo Chen, Zhuo-Yuan Lin, Xin Fu, Xiao-Hui Ling, Zhao-Dong Han, Fu-Neng Jiang, Wei-De Zhong
• Journal: International journal of biological macromolecules (Int J Biol Macromol) Vol. 81 Pg. 615-23 (Nov 2015) ISSN: 1879-0003 [Electronic] Netherlands
• PMID: 26314905 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• E2F1 Transcription Factor
• Mitogen-Activated Protein Kinase Kinases
• PDZ-binding kinase

Topics

• Aged
• Aged, 80 and over
• Base Sequence
• Binding Sites
• Cell Line, Tumor
• Cell Movement
• Cell Survival
• Cytoprotection
• Disease Progression
• E2F1 Transcription Factor (metabolism)
• Gene Expression Regulation, Neoplastic
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Mitogen-Activated Protein Kinase Kinases (genetics, metabolism)
• Neoplasm Grading
• Neoplasm Staging
• Nucleotide Motifs
• Phenotype
• Prognosis
• Promoter Regions, Genetic
• Prostatic Neoplasms (genetics, metabolism, mortality, pathology)
• Protein Binding