title: JNK2 downregulation promotes tumorigenesis and chemoresistance by decreasing p53 stability in bladder cancer.
abstract: Bladder cancer is one of the most common malignancies of the urinary system, and the 5-year survival rate remains low. A comprehensive understanding of the carcinogenesis and progression of bladder cancer is urgently needed to advance treatment. c-Jun N-terminal kinase-2 (JNK2) exhibits both tumor promoter and tumor suppressor actions, depending on tumor type. Here, we analyzed the JNK2 function in bladder cancer. Using gene expression microarrays, we demonstrated that JNK2 mRNA is downregulated in an orthotopic rat model of bladder cancer. JNK2 protein levels were lower in rat and human bladder cancer tissues than in normal tissues, and the levels correlated with those of p53. Moreover, JNK2 phosphorylated p53 at Thr-81, thus protecting p53 from MDM2-induced proteasome degradation. Decreased expression of JNK2 in T24 cells conferred resistance to cell death induced by mitomycin C. Furthermore, lower JNK2 expression was associated with poorer overall survival among patients who underwent radical cystectomy. These results indicate that JNK2 acts as a tumor suppressor in bladder cancer, and that decreased JNK2 expression promotes bladder cancer tumorigenesis.
authors.affiliation: Department of Urology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Huangpu, Shanghai 200092, China.
authors.forename: Chun-Wu
authors.initials: CW
authors.lastname: Pan
authors.affiliation: Department of Urology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Huangpu, Shanghai 200092, China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, US.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Qian
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, MN 55905, US.
authors.forename: Liguo
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Urology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Huangpu, Shanghai 200092, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qi
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism*; D055550:Protein Stability; D051381:Rats; D017207:Rats, Sprague-Dawley; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D048056:Mitogen-Activated Protein Kinase 9
keywords: JNK2; bladder cancer; chemoresistance; p53; tumorigenesis