Activator Protein-1 Transcription Factors Are Associated with Progression and Recurrence of Prostate Cancer
| Autor: | Victor E. Reuter, Cory Abate-Shen, Angel M. Serio, Peter T. Scardino, Hikmat Al-Ahmadie, Walter J. Jessen, Xuesong Ouyang, William L. Gerald, Yong Lin, Andrew J. Vickers, Bruce J. Aronow, Weichung-Joseph Shih, Michael M. Shen |
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| Rok vydání: | 2008 |
| Předmět: |
Male
MAPK/ERK pathway Cancer Research MAP Kinase Signaling System Oncogene Protein p65(gag-jun) Biology Mice Prostate cancer Epidermal growth factor medicine Animals PTEN Transcription factor Homeodomain Proteins Mitogen-Activated Protein Kinase Kinases Epidermal Growth Factor Activator (genetics) Kinase Gene Expression Profiling PTEN Phosphohydrolase Prostatic Neoplasms medicine.disease Mice Mutant Strains Enzyme Activation Gene Expression Regulation Neoplastic Transcription Factor AP-1 Disease Models Animal Oncology Disease Progression Cancer research biology.protein Neoplasm Recurrence Local Signal transduction Proto-Oncogene Proteins c-fos Transcription Factors |
| Zdroj: | Cancer Research. 68:2132-2144 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | 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] |
| Databáze: | OpenAIRE |
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