This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ouyang, X. Articles by Abate-Shen, C. Search for Related Content PubMed PubMed Citation Articles by Ouyang, X. Articles by Abate-Shen, C.

Activator Protein-1 Transcription Factors Are Associated with Progression and Recurrence of Prostate Cancer

¹ Center for Advanced Biotechnology and Medicine, Departments of ² Medicine, ³ Pediatrics, and ⁴ Biometrics, ⁵ The Cancer Institute of New Jersey, University of Medicine and Dentistry, New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey; ⁶ Department of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio; Departments of ⁷ Pathology, ⁸ Surgery (Urology), ⁹ Human Oncology and Pathogenesis, and ¹⁰ Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York

Requests for reprints: Cory Abate-Shen, Department of Urology, Columbia University, College of Physicians and Surgeons, Herbert Irving Comprehensive Cancer Center, 1130 St. Nicholas Avenue, Room 217A, New York, NY 10032. Phone: 212-851-4731; Fax: 212-851-4572; E-mail: cabateshen{at}columbia.edu.

Key Words: AP-1 • mouse models • prostate cancer

To identify biomarkers that discriminate the aggressive forms of prostate cancer, we performed gene expression profiling of prostate tumors using a genetically engineered mouse model that recapitulates the stages of human prostate cancer, namely Nkx3.1; Pten mutant mice. We observed a significant deregulation of the epidermal growth factor and mitogen-activated protein kinase (MAPK) signaling pathways, as well as their major downstream effectors—the activator protein-1 transcription factors c-Fos and c-Jun. Forced expression of c-Fos and c-Jun in prostate cancer cells promotes tumorigenicity and results in activation of extracellular signal-regulated kinase (Erk) MAPK signaling. In human prostate cancer, up-regulation of c-Fos and c-Jun proteins occurs in advanced disease and is correlated with Erk MAPK pathway activation, whereas high levels of c-Jun expression are associated with disease recurrence. Our analyses reveal a hitherto unappreciated role for AP-1 transcription factors in prostate cancer progression and identify c-Jun as a marker of high-risk prostate cancer. This study provides a striking example of how accurate mouse models can provide insights on molecular processes involved in progression and recurrence of human cancer. [Cancer Res 2008;68(7):2132–44]

This article has been cited by other articles:

				S. Jain, G. Chakraborty, R. Raja, S. Kale, and G. C. Kundu Prostaglandin E2 Regulates Tumor Angiogenesis in Prostate Cancer Cancer Res., October 1, 2008; 68(19): 7750 - 7759. [Abstract] [Full Text] [PDF]

				T. Boutros, E. Chevet, and P. Metrakos Mitogen-Activated Protein (MAP) Kinase/MAP Kinase Phosphatase Regulation: Roles in Cell Growth, Death, and Cancer Pharmacol. Rev., September 1, 2008; 60(3): 261 - 310. [Abstract] [Full Text] [PDF]

				C. Abate-Shen, P. H. Brown, N. H. Colburn, E. W. Gerner, J. E. Green, M. Lipkin, W. G. Nelson, and D. Threadgill The Untapped Potential of Genetically Engineered Mouse Models in Chemoprevention Research: Opportunities and Challenges Cancer Prevention Research, August 1, 2008; 1(3): 161 - 166. [Abstract] [Full Text] [PDF]