JNK and PTEN cooperatively control the development of invasive adenocarcinoma of the prostate

Anette Hübner, David J. Mulholland, Claire L. Standen, Maria Karasarides, Julie Cavanagh-Kyros, Tamera Barrett, Hongbo Chi, Dale L. Greiner, Cathy Tournier, Charles L. Sawyers, Richard A. Flavell, Hong Wu, Roger J. Davis

Research output: Contribution to journalArticlepeer-review

79 Scopus citations


The c-Jun NH2-terminal kinase (JNK) signal transduction pathway is implicated in cancer, but the role of JNK in tumorigenesis is poorly understood. Here, we demonstrate that the JNK signaling pathway reduces the development of invasive adenocarcinoma in the phosphatase and tensin homolog (Pten) conditional deletion model of prostate cancer. Mice with JNK deficiency in the prostate epithelium (ΔJnk ΔPten mice) develop androgen-independent metastatic prostate cancer more rapidly than control (ΔPten) mice. Similarly, prevention of JNK activation in the prostate epithelium (ΔMkk4 ΔMkk7 ΔPten mice) causes rapid development of invasive adenocarcinoma. We found that JNK signaling defects cause an androgen-independent expansion of the immature progenitor cell population in the primary tumor. The JNK-deficient progenitor cells display increased proliferation and tumorigenic potential compared with progenitor cells from control prostate tumors. These data demonstrate that the JNK and PTEN signaling pathways can cooperate to regulate the progression of prostate neoplasia to invasive adenocarcinoma.

Original languageEnglish
Pages (from-to)12046-12051
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number30
StatePublished - 24 Jul 2012
Externally publishedYes


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