UMMS Affiliation

Program in Molecular Medicine

Date

7-24-2012

Document Type

Article

Medical Subject Headings

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

Disciplines

Biochemistry | Cancer Biology | Cell Biology | Cellular and Molecular Physiology | Molecular Biology

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 (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

Citation: 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

Comments

Freely available online through the PNAS open access option.

Related Resources

Link to Article in PubMed

PubMed ID

22753496

 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.