title: Telomere length modulation in human astroglial brain tumors.
abstract: BACKGROUND
  Telomeres alteration during carcinogenesis and tumor progression has been described in several cancer types. Telomeres length is stabilized by telomerase (h-TERT) and controlled by several proteins that protect telomere integrity, such as the Telomere Repeat-binding Factor (TRF) 1 and 2 and the tankyrase-poli-ADP-ribose polymerase (TANKs-PARP) complex.
  
  
  OBJECTIVE
  To investigate telomere dysfunction in astroglial brain tumors we analyzed telomeres length, telomerase activity and the expression of a panel of genes controlling the length and structure of telomeres in tissue samples obtained in vivo from astroglial brain tumors with different grade of malignancy.
  
  
  METHODS
  Eight Low Grade Astrocytomas (LGA), 11 Anaplastic Astrocytomas (AA) and 11 Glioblastoma Multiforme (GBM) samples were analyzed. Three samples of normal brain tissue (NBT) were used as controls. Telomeres length was assessed through Southern Blotting. Telomerase activity was evaluated by a telomere repeat amplification protocol (TRAP) assay. The expression levels of TRF1, TRF2, h-TERT and TANKs-PARP complex were determined through Immunoblotting and RT-PCR.
  
  
  RESULTS
  LGA were featured by an up-regulation of TRF1 and 2 and by shorter telomeres. Conversely, AA and GBM were featured by a down-regulation of TRF1 and 2 and an up-regulation of both telomerase and TANKs-PARP complex.
  
  
  CONCLUSIONS
  In human astroglial brain tumours, up-regulation of TRF1 and TRF2 occurs in the early stages of carcinogenesis determining telomeres shortening and genomic instability. In a later stage, up-regulation of PARP-TANKs and telomerase activation may occur together with an ADP-ribosylation of TRF1, causing a reduced ability to bind telomeric DNA, telomeres elongation and tumor malignant progression.
authors.affiliation: Department of Neurosciences, University of Messina School of Medicine, Messina, Italy. dlatorre@unime.it
authors.forename: Domenico
authors.initials: D
authors.lastname: La Torre
authors.forename: Alfredo
authors.initials: A
authors.lastname: Conti
authors.forename: M Hammed
authors.initials: MH
authors.lastname: Aguennouz
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: De Pasquale
authors.forename: Sara
authors.initials: S
authors.lastname: Romeo
authors.forename: Filippo Flavio
authors.initials: FF
authors.lastname: Angileri
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cardali
authors.forename: Chiara
authors.initials: C
authors.lastname: Tomasello
authors.forename: Concetta
authors.initials: C
authors.lastname: Alafaci
authors.forename: Antonino
authors.initials: A
authors.lastname: Germanò
mesh_terms: D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics; D038501:Tankyrases / Q000235:genetics; D019098:Telomerase / Q000235:genetics; D016615:Telomere / Q000235:genetics*; D035321:Telomeric Repeat Binding Protein 1 / Q000235:genetics; D035341:Telomeric Repeat Binding Protein 2 / Q000235:genetics
chemical_list: D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2; D011065:Poly(ADP-ribose) Polymerases; D038501:Tankyrases; D019098:Telomerase