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.
Written by:
Hübner A, Mulholland DJ, Standen CL, Karasarides M, Cavanagh-Kyros J, Barrett T, Chi H, Greiner DL, Tournier C, Sawyers CL, Flavell RA, Wu H, Davis RJ. Are you the author?
Program in Molecular Medicine, University of Massachusetts Medical School, and Howard Hughes Medical Institute, Worcester, MA 01605.
Reference: Proc Natl Acad Sci U S A. 2012 Jul 24;109(30):12046-51.
doi: 10.1073/pnas.1209660109
PubMed Abstract
PMID: 22753496
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