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.
authors.affiliation: Center for Advanced Biotechnology and Medicine, University of Medicine and Dentistry, New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey, USA.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Ouyang
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Jessen
authors.forename: Hikmat
authors.initials: H
authors.lastname: Al-Ahmadie
authors.forename: Angel M
authors.initials: AM
authors.lastname: Serio
authors.forename: Yong
authors.initials: Y
authors.lastname: Lin
authors.forename: Weichung-Joseph
authors.initials: WJ
authors.lastname: Shih
authors.forename: Victor E
authors.initials: VE
authors.lastname: Reuter
authors.forename: Peter T
authors.initials: PT
authors.lastname: Scardino
authors.forename: Michael M
authors.initials: MM
authors.lastname: Shen
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Aronow
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Vickers
authors.forename: William L
authors.initials: WL
authors.lastname: Gerald
authors.forename: Cory
authors.initials: C
authors.lastname: Abate-Shen
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016759:Oncogene Protein p65(gag-jun) / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; C102837:Nkx3-1 protein, mouse; D016759:Oncogene Protein p65(gag-jun); D016760:Proto-Oncogene Proteins c-fos; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D004815:Epidermal Growth Factor; D020929:Mitogen-Activated Protein Kinase Kinases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse