Abstract |
The c-Jun NH(2)-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.
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Authors | 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 |
Journal | Proceedings of the National Academy of Sciences of the United States of America
(Proc Natl Acad Sci U S A)
Vol. 109
Issue 30
Pg. 12046-51
(Jul 24 2012)
ISSN: 1091-6490 [Electronic] United States |
PMID | 22753496
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- JNK Mitogen-Activated Protein Kinases
- PTEN Phosphohydrolase
- Pten protein, mouse
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Topics |
- Adenocarcinoma
(physiopathology)
- Animals
- Cell Transformation, Neoplastic
(metabolism)
- Histological Techniques
- JNK Mitogen-Activated Protein Kinases
(metabolism)
- MAP Kinase Signaling System
(physiology)
- Male
- Mice
- Mice, Transgenic
- Microscopy, Fluorescence
- PTEN Phosphohydrolase
(metabolism)
- Prostatic Neoplasms
(physiopathology)
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