title: DKC1 overexpression associated with prostate cancer progression.
abstract: BACKGROUND
  Dyskerin encoded by the DKC1 gene is a predominantly nucleolar protein essential for the formation of pseudouridine in RNA and the telomerase RNA subunit hTR. Inherited mutations inactivating dyskerin cause dyskeratosis congenita, a syndrome with progeroid features characterised by skin defects and haematopoiesis failure, as well as cancer susceptibility. In this study, we report DKC1 overexpression in prostate cancers.
  
  
  METHODS
  Expression of DKC1 was measured by quantitative RT-PCR in prostate cancer tissues in relation to hTR and the proliferation marker MKI67. Effects of dyskerin downregulation on proliferation, apoptosis and senescence of prostate cancer cell lines were determined.
  
  
  RESULTS
  DKC1 was significantly overexpressed in prostate cancers, particularly in high-stage and recurring cases, correlating moderately with hTR and MKI67. Dyskerin downregulation in prostate carcinoma cell lines by siRNA diminished cell proliferation, but elicited neither apoptosis nor senescence. Apoptosis induction by TNF-alpha or tunicamycin was not enhanced. Long-term downregulation led predominantly to cell shrinking and loss of adhesion.
  
  
  CONCLUSIONS
  DKC1 upregulation in prostate cancers is common and likely to be necessary for extensive tumour growth. The phenotype of prostate carcinoma cell lines after dyskerin downregulation suggests that its most critical function is sustaining protein biosynthesis. Intriguingly, compromised function and overexpression of dyskerin can both contribute to cancer development.
authors.affiliation: Urologische Klinik, Heinrich Heine Universität, Düsseldorf, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Sieron
authors.forename: C
authors.initials: C
authors.lastname: Hader
authors.forename: J
authors.initials: J
authors.lastname: Hatina
authors.forename: R
authors.initials: R
authors.lastname: Engers
authors.forename: A
authors.initials: A
authors.lastname: Wlazlinski
authors.forename: M
authors.initials: M
authors.lastname: Müller
authors.forename: W A
authors.initials: WA
authors.lastname: Schulz
mesh_terms: D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D018450:Disease Progression; D006801:Humans; D008297:Male; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D034741:RNA, Small Interfering / Q000235:genetics; D019098:Telomerase / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; C112148:DKC1 protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019098:Telomerase