Telomere length modulation in human astroglial brain tumors

• Published in: PloS one 2013-05, Vol.8 (5), p.e64296
• Main Authors: La Torre, Domenico, Conti, Alfredo, Aguennouz, M Hammed, De Pasquale, Maria Grazia, Romeo, Sara, Angileri, Filippo Flavio, Cardali, Salvatore, Tomasello, Chiara, Alafaci, Concetta, Germanò, Antonino
• Format: Article
• Language: English
• Subjects: Acid phosphatase (tartrate-resistant); Adenosine diphosphate; ADP-ribosylation; Adult; Aged; Analysis; Astrocytoma; Astrocytoma - enzymology; Astrocytoma - genetics; Astrocytoma - pathology; Brain; Brain cancer; Brain Neoplasms - enzymology; Brain Neoplasms - genetics; Brain Neoplasms - pathology; Brain tumors; Cancer; Carcinogenesis; Carcinogens; Cell division; Chromosomes; Deoxyribonucleic acid; Development and progression; Disease Progression; DNA; Elongation; Ethics; Female; Gene expression; Gene Expression Regulation, Neoplastic; Genes; Genomic instability; Glioblastoma; Glioblastoma - enzymology; Glioblastoma - genetics; Glioblastoma - pathology; Glioblastoma multiforme; Homeostasis; Humans; Immunoblotting; Male; Malignancy; Medical prognosis; Medicine; Middle Aged; Monosaccharides; Neoplasm Grading; Neoplasm Staging; Neurosciences; Patients; Poly(ADP-ribose) polymerase; Poly(ADP-ribose) Polymerases - genetics; Polymerase chain reaction; Proteins; Quality; Regulations; Ribose; Ribosylation; Senescence; Southern blotting; Stability; Studies; Tanks; Tankyrases - genetics; Telomerase; Telomerase - genetics; Telomere - genetics; Telomere-binding protein; Telomeres; Telomeric Repeat Binding Protein 1 - genetics; Telomeric Repeat Binding Protein 2 - genetics; TRF2 protein; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0064296

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. 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. 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. 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. 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.