JNK and PTEN cooperatively control the development of invasive adenocarcinoma of the prostate
Authors
Hubner, AnetteMulholland, 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
Davis, Roger J.
UMass Chan Affiliations
Program in Molecular MedicineDocument Type
Journal ArticlePublication Date
2012-07-24Keywords
AdenocarcinomaAnimals
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
Metadata
Show full item recordAbstract
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.Source
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 siteDOI
10.1073/pnas.1209660109Permanent Link to this Item
http://hdl.handle.net/20.500.14038/28315PubMed ID
22753496Related Resources
Link to Article in PubMedRights
Freely available online through the PNAS open access option.
ae974a485f413a2113503eed53cd6c53
10.1073/pnas.1209660109