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


Authors: Ouyang, X.; Jessen, W. J.; Al-Ahmadie, H.; Serio, A. M.; Lin, Y.; Shih, W. J.; Reuter, V. E.; Scardino, P. T.; Shen, M. M.; Aronow, B. J.; Vickers, A. J.; Gerald, W. L.; Abate-Shen, C.
Article Title: Activator protein-1 transcription factors are associated with progression and recurrence of prostate cancer
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. ©2008 American Association for Cancer Research.
Keywords: epidermal growth factor; mitogen activated protein kinase; controlled study; human tissue; protein expression; cancer recurrence; advanced cancer; cancer growth; cancer risk; nonhuman; animal cell; mouse; animals; mice; neoplasm recurrence, local; gene expression profiling; map kinase signaling system; animal experiment; animal model; mice, mutant strains; homeodomain proteins; enzyme activation; carcinogenesis; transcription factors; prostate cancer; prostatic neoplasms; gene expression regulation, neoplastic; genetic engineering; disease progression; cancer cell; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; carcinogenicity; pten phosphohydrolase; upregulation; disease models, animal; mitogen-activated protein kinase kinases; transcription factor ap 1; protein c fos; proto-oncogene proteins c-fos; protein c jun; oncogene protein p65(gag-jun); transcription factor ap-1
Journal Title: Cancer Research
Volume: 68
Issue: 7
ISSN: 0008-5472
Publisher: American Association for Cancer Research  
Date Published: 2008-04-01
Start Page: 2132
End Page: 2144
Language: English
DOI: 10.1158/0008-5472.can-07-6055
PUBMED: 18381418
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 29" - "Export Date: 17 November 2011" - "CODEN: CNREA" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Peter T Scardino
    622 Scardino
  2. William L Gerald
    370 Gerald
  3. Andrew J Vickers
    569 Vickers
  4. Angel M Cronin
    145 Cronin
  5. Victor Reuter
    926 Reuter