Program in Molecular Medicine
Adenocarcinoma; Animals; Cell Transformation, Neoplastic; Histological Techniques; JNK Mitogen-Activated Protein Kinases; MAP Kinase Signaling System; Male; Mice; Mice, Transgenic; Microscopy, Fluorescence; PTEN Phosphohydrolase; Prostatic Neoplasms
Biochemistry | Cancer Biology | Cell Biology | Cellular and Molecular Physiology | Molecular Biology
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 (DeltaJnk DeltaPten mice) develop androgen-independent metastatic prostate cancer more rapidly than control (DeltaPten) mice. Similarly, prevention of JNK activation in the prostate epithelium (DeltaMkk4 DeltaMkk7 DeltaPten 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.
Rights and Permissions
Freely available online through the PNAS open access option.
DOI of Published Version
Proc Natl Acad Sci U S A. 2012 Jul 24;109(30):12046-51. doi: 10.1073/pnas.1209660109. Epub 2012 Jul 2. Link to article on publisher's site
Proceedings of the National Academy of Sciences of the United States of America
Hubner, Anette; Mulholland, David J.; Standen, Claire L.; Karasarides, Maria; Cavanagh-Kyros, Julie; Barrett, Tamera; Chi, Hongbo; Greiner, Dale; Tournier, Cathy; Sawyers, Charles L.; Flavell, Richard A.; Wu, Hong; and Davis, Roger J., "JNK and PTEN cooperatively control the development of invasive adenocarcinoma of the prostate" (2012). Davis Lab Publications. 43.