JNK2 downregulation promotes tumorigenesis and chemoresistance by decreasing p53 stability in bladder cancer

Chun Wu Pan, Hailong Liu, Yu Zhao, Chenchen Qian, Liguo Wang, Jun Qi

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)35119-35131
Number of pages13
JournalOncotarget
Volume7
Issue number23
DOIs
StatePublished - Jun 7 2016

Fingerprint

Mitogen-Activated Protein Kinase 9
Urinary Bladder Neoplasms
Carcinogenesis
Down-Regulation
Neoplasms
Cystectomy
Mitomycin
Proteasome Endopeptidase Complex
Carcinogens
Cell Death
Survival Rate

Keywords

  • Bladder cancer
  • Chemoresistance
  • JNK2
  • P53
  • Tumorigenesis

ASJC Scopus subject areas

  • Oncology

Cite this

JNK2 downregulation promotes tumorigenesis and chemoresistance by decreasing p53 stability in bladder cancer. / Pan, Chun Wu; Liu, Hailong; Zhao, Yu; Qian, Chenchen; Wang, Liguo; Qi, Jun.

In: Oncotarget, Vol. 7, No. 23, 07.06.2016, p. 35119-35131.

Research output: Contribution to journalArticle

Pan, Chun Wu ; Liu, Hailong ; Zhao, Yu ; Qian, Chenchen ; Wang, Liguo ; Qi, Jun. / JNK2 downregulation promotes tumorigenesis and chemoresistance by decreasing p53 stability in bladder cancer. In: Oncotarget. 2016 ; Vol. 7, No. 23. pp. 35119-35131.
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