title: Function of JunB in transient amplifying cell senescence and progression of human prostate cancer.
abstract: OBJECTIVE
  Replicative senescence in cells acts as a barrier against excessive proliferation and carcinogenesis. Transient amplifying cells (TAC) are a subset of basal cell populations within the prostate from which cancers are thought to originate; therefore, we focused on prostate TAC to investigate the molecular mechanisms by which the TAC may be able to evade senescence.
  
  
  METHODS
  TAC clones were isolated from each zone within the whole prostate and analyzed in flow cytometry. Prostate cancer cells were transfected with junB small interfering RNA (siRNA) and examined by chorioallantoic membrane assay for cancer invasion. Immunohistochemical analysis was done in primary and metastatic prostate cancer specimens.
  
  
  RESULTS
  TAC populations showed increased expression of p53, p21, p16, and pRb, resulting in senescence. TAC clones with reduced p16 expression successfully bypassed this phase. We further found close correlation between the levels of junB and p16 expression. Repeated transfection of junB siRNA in prostatic TAC allowed the cells to escape senescence presumably through inactivation of p16/pRb. The chorioallantoic membrane invasion assay showed much lower in invasive cancer cells with high expression of junB; conversely, silencing of junB by transfection with junB siRNA promoted invasion. We also found that metastatic prostate cancers, as well as cancers with high Gleason scores, showed significantly low junB immunopositivity.
  
  
  CONCLUSIONS
  JunB is an essential upstream regulator of p16 and contributes to maintain cell senescence that blocks malignant transformation of TAC. JunB thus apparently plays an important role in controlling prostate carcinogenesis and may be a new target for cancer prevention and therapy.
authors.affiliation: Department of Pathology, Nara Medical University School of Medicine, Nara, Japan. nkonishi@naramed-u.ac.jp
authors.forename: Noboru
authors.initials: N
authors.lastname: Konishi
authors.forename: Keiji
authors.initials: K
authors.lastname: Shimada
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Nakamura
authors.forename: Eiwa
authors.initials: E
authors.lastname: Ishida
authors.forename: Ichiro
authors.initials: I
authors.lastname: Ota
authors.forename: Nobumichi
authors.initials: N
authors.lastname: Tanaka
authors.forename: Kiyohide
authors.initials: K
authors.lastname: Fujimoto
mesh_terms: D000368:Aged; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016922:Cellular Senescence / Q000502:physiology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D018450:Disease Progression; D005434:Flow Cytometry; D015870:Gene Expression; D016758:Genes, jun / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D034741:RNA, Small Interfering; D016160:Retinoblastoma Protein / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D034741:RNA, Small Interfering; D016160:Retinoblastoma Protein