title: JNK and PTEN cooperatively control the development of invasive adenocarcinoma of the prostate.
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.
authors: University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors: Anette
authors: A
authors: Hübner
authors: David J
authors: DJ
authors: Mulholland
authors: Claire L
authors: CL
authors: Standen
authors: Maria
authors: M
authors: Karasarides
authors: Julie
authors: J
authors: Cavanagh-Kyros
authors: Tamera
authors: T
authors: Barrett
authors: Hongbo
authors: H
authors: Chi
authors: Dale L
authors: DL
authors: Greiner
authors: Cathy
authors: C
authors: Tournier
authors: Charles L
authors: CL
authors: Sawyers
authors: Richard A
authors: RA
authors: Flavell
authors: Hong
authors: H
authors: Wu
authors: Roger J
authors: RJ
authors: Davis
mesh_terms: D000230:Adenocarcinoma / Q000503:physiopathology*; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D006652:Histological Techniques; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000503:physiopathology*
chemical_list: D048031:JNK Mitogen-Activated Protein Kinases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse