| First Author | Ouyang X | Year | 2008 |
| Journal | Cancer Res | Volume | 68 |
| Issue | 7 | Pages | 2132-44 |
| PubMed ID | 18381418 | Mgi Jnum | J:133304 |
| Mgi Id | MGI:3778242 | Doi | 10.1158/0008-5472.CAN-07-6055 |
| Citation | Ouyang X, et al. (2008) Activator protein-1 transcription factors are associated with progression and recurrence of prostate cancer. Cancer Res 68(7):2132-44 |
| abstractText | 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. |
