Activator protein-1 transcription factors are associated with progression and recurrence of prostate cancer

Xuesong Ouyang, Walter J. Jessen, Hikmat Al-Ahmadie, Angel M. Serio, Yong Lin, Weichung Joseph Shih, Victor E. Reuter, Peter T. Scardino, Michael M. Shen, Bruce J. Aronow, Andrew J. Vickers, William L. Gerald, Cory Abate-Shen

Research output: Contribution to journalArticlepeer-review

96 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2132-2144
Number of pages13
JournalCancer Research
Volume68
Issue number7
DOIs
StatePublished - Apr 1 2008

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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